bluuebunny/crossref_metadata_2025 huggingface dataset:
Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice
Authors: Zhang Ying , Si Yanhong , Zhai Lei , Guo Shoudong , Zhao Jilong , Sang Hui , Pang Xiaofei , Zhang Xue , Chen Anbin , Qin Shucun
Published: March 2016

Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero‐susceptibility in lipoproteins and the aorta of guinea pigs fed a high‐fat diet, and increases high‐density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high‐fat diet alone, high‐fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. Serum levels of total cholesterol (TC), triglyceride (TG), HDL‐C, non‐HDL‐C, and 3H‐cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and TG in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non‐HDL‐C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL‐C and apolipoprotein A (apoA1). 3H‐cholesterol in plasma, liver, bile, and feces was also significantly increased in COT‐treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP‐binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT‐treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of 3H‐cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.
Preoperative halo-gravity traction with and without thoracoscopic anterior release for skeletal dysplasia patients with severe kyphoscoliosis
Authors: Pourtaheri Sina , Shah Suken A. , Ditro Colleen P. , Holmes Laurens , Mackenzie William G.
Published: March 2016

Purpose

Recent work has shown the safety and efficacy of halo-gravity traction as an operative adjunct. However, there are no reports specifically looking at halo-gravity traction in patients with skeletal dysplasia. Our purpose was to assess the safety and efficacy of traction in children with skeletal dysplasia who present with severe kyphoscoliosis.

Methods

We retrospectively reviewed eight consecutive children with skeletal dysplasia who were treated with halo-gravity traction preoperatively. Six of the patients had a thoracoscopic anterior release prior to the halo-gravity traction. All patients were ambulatory and presented with severe, rigid kyphoscoliosis.

Results

The mean duration of traction was 32 days. There were no neurologic complications with traction or after posterior spinal instrumentation. The majority of kyphoscoliosis correction was with the halo-gravity traction alone: major curve (MC) Cobb angle improved 41 %; C7–center sacral vertical line, 75 %; C7–MC apex, 21 %; and T2–T12 kyphosis, 35 %. Trunk height increased 37 % and thoracic height 44 %. An additional amount of correction was obtained with posterior spinal instrumentation (±fusion), decreasing MC Cobb angle an additional 23 %; C7–apex, 16 %; and T2–T12 kyphosis, 10 %. There was no additional correction of thoracic height. Two years after posterior spinal instrumentation (±fusion), a mild-to-moderate amount of correction was lost: MC Cobb angle decreased 23 %; compensatory Cobb angle, 28 %; C7–CSVL, 24 %; C7–S1, 22 %; regional kyphosis, 31 %; thoracic kyphosis, 29 %; and trunk height, 27 %.

Conclusions

Among children with skeletal dysplasia and severe kyphosis, halo-gravity traction is well tolerated and safe. Most of the corrections in radiographic parameters were achieved with traction alone. Traction improves coronal balance, apical translation, thoracic height, and kyphosis. In this specific population, the potential for neurologic injury during corrective surgery is high. However, preoperative halo-gravity traction provides slow, progressive correction in a safe manner and avoided neurologic injury in these patients. This study did not compare patients without halo-gravity traction to patients with halo-gravity traction, therefore it cannot be concluded that going straight to instrumentation without traction will give a poorer radiographic result.

Level of evidence

IV.
SORLA regulates calpain‐dependent degradation of synapsin
Authors: Hartl Daniela , Nebrich Grit , Klein Oliver , Stephanowitz Heike , Krause Eberhard , Rohe Michael
Published: March 2016

Introduction

Sorting‐related receptor with A‐type repeats (SORLA) is an intracellular sorting receptor in neurons and a major risk factor for Alzheimer disease.

Methods

Here, we performed global proteome analyses in the brain of SORLA‐deficient mice followed by biochemical and histopathologic studies to identify novel neuronal pathways affected by receptor dysfunction.

Results

We demonstrate that the lack of SORLA results in accumulation of phosphorylated synapsins in cortex and hippocampus. We propose an underlying molecular mechanism by demonstrating that SORLA interacts with phosphorylated synapsins through 14‐3‐3 adaptor proteins to deliver synapsins to calpain‐mediated proteolytic degradation.

Discussion

Our results suggest a novel function for SORLA which is in control of synapsin degradation, potentially impacting on synaptic vesicle endocytosis and/or exocytosis.
Motion-capture-based walking simulation of digital human adapted to laser-scanned 3D as-is environments for accessibility evaluation
Authors: Maruyama Tsubasa , Kanai Satoshi , Date Hiroaki , Tada Mitsunori
Published: March 2016

Owing to our rapidly aging society, accessibility evaluation to enhance the ease and safety of access to indoor and outdoor environments for the elderly and disabled is increasing in importance. Accessibility must be assessed not only from the general standard aspect but also in terms of physical and cognitive friendliness for users of different ages, genders, and abilities. Meanwhile, human behavior simulation has been progressing in the areas of crowd behavior analysis and emergency evacuation planning. However, in human behavior simulation, environment models represent only “as-planned” situations. In addition, a pedestrian model cannot generate the detailed articulated movements of various people of different ages and genders in the simulation. Therefore, the final goal of this research was to develop a virtual accessibility evaluation by combining realistic human behavior simulation using a digital human model (DHM) with “as-is” environment models. To achieve this goal, we developed an algorithm for generating human-like DHM walking motions, adapting its strides, turning angles, and footprints to laser-scanned 3D as-is environments including slopes and stairs. The DHM motion was generated based only on a motion-capture (MoCap) data for flat walking. Our implementation constructed as-is 3D environment models from laser-scanned point clouds of real environments and enabled a DHM to walk autonomously in various environment models. The difference in joint angles between the DHM and MoCap data was evaluated. Demonstrations of our environment modeling and walking simulation in indoor and outdoor environments including corridors, slopes, and stairs are illustrated in this study.

Highlights An adaptive walking simulation algorithm of the digital human was developed. The environment models are automatically generated from laser-scanned point clouds. A digital human can walk autonomously in various as-built environment models. Simulated walking motion of the digital human is similar to one of real human. Elapsed time of modeling and simulation is short enough for practical application.
La medicina natural y tradicional y su relación con las ciencias básicas
Authors: Vidor Guerra Elizabeth , Padilla Rodríguez Elaine , Guerrero Betancourt Mayren
Published: March 2016

Estimado editor creo que es importante abordar el tema de la medicina tradicional natural (MTN) ya que esta constituye un sistema de conocimiento armónicamente estructurado, que como toda ciencia contribuye al conocimiento del mundo circundante, en este caso, de forma especial a la salud humana.
High-Resolution Climate Modeling for Regional Adaptation
Authors: Rangwala Imtiaz , Dewes Candida , Barsugli Joseph
Published: March 2016

High-Resolution Climate Modeling in the Northern Great Plains; Boulder, Colorado, 24–25 September 2015
Navy Ship Mysteriously Lost in 1921 Found via Science, Sleuthing
Authors: Showstack Randy
Published: March 2016

Scientists painstakingly compared a shipwreck spotted in 2009 to a 1904 schematic of a long-lost tugboat. A naval gun on the wreck proved to be the "smoking gun" identifying the vanished ship.
Charge transfer in dissociating iodomethane and fluoromethane molecules ionized by intense femtosecond X-ray pulses
Authors: Boll Rebecca , Erk Benjamin , Coffee Ryan , Trippel Sebastian , Kierspel Thomas , Bomme Cédric , Bozek John D. , Burkett Mitchell , Carron Sebastian , Ferguson Ken R. , Foucar Lutz , Küpper Jochen , Marchenko Tatiana , Miron Catalin , Patanen Minna , Osipov Timur , Schorb Sebastian , Simon Marc , Swiggers Michelle , Techert Simone , Ueda Kiyoshi , Bostedt Christoph , Rolles Daniel , Rudenko Artem
Published: March 2016

Ultrafast electron transfer in dissociating iodomethane and fluoromethane molecules was studied at the Linac Coherent Light Source free-electron laser using an ultraviolet-pump, X-ray-probe scheme. The results for both molecules are discussed with respect to the nature of their UV excitation and different chemical properties. Signatures of long-distance intramolecular charge transfer are observed for both species, and a quantitative analysis of its distance dependence in iodomethane is carried out for charge states up to I21+. The reconstructed critical distances for electron transfer are in good agreement with a classical over-the-barrier model and with an earlier experiment employing a near-infrared pump pulse.
Between syntax and discourse
Authors: Laleko Oksana , Polinsky Maria
Published: March 2016

This article examines the knowledge of topic and subject particles in heritage speakers and L2 learners of Japanese and Korean. We assume that topic marking is mediated at the syntax-information structure interface, while subject marking pertains to narrow syntax. In comparing phenomena mediated at different levels of linguistic organization, we provide evidence for the hypothesis that information structure-level phenomena present greater challenges for bilingual speakers than those mediated within syntax. While these results may be interpreted as evidence of generalized interface-related deficits, we show that such a global explanation is not supported. Instead, a more nuanced account is developed, based on the recognition of different types of topic (anaphoric, generic, and contrastive) and different types of subject (descriptive and exhaustive). Under the proposed account, non-native speakers’ deficits follow from three unrelated effects: the status of topic as an interface category, structural complexity, and the memory demands necessary for its interpretation in context.
PinSnps: structural and functional analysis of SNPs in the context of protein interaction networks
Authors: Lu Hui-Chun , Herrera Braga Julián , Fraternali Franca
Published: March 2016

Summary: We present a practical computational pipeline to readily perform data analyses of protein–protein interaction networks by using genetic and functional information mapped onto protein structures. We provide a 3D representation of the available protein structure and its regions (surface, interface, core and disordered) for the selected genetic variants and/or SNPs, and a prediction of the mutants’ impact on the protein as measured by a range of methods. We have mapped in total 2587 genetic disorder-related SNPs from OMIM, 587 873 cancer-related variants from COSMIC, and 1 484 045 SNPs from dbSNP. All result data can be downloaded by the user together with an R-script to compute the enrichment of SNPs/variants in selected structural regions.

Availability and Implementation: PinSnps is available as open-access service at http://fraternalilab.kcl.ac.uk/PinSnps/

Contact:  franca.fraternali@kcl.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
FREGAT: an R package for region-based association analysis
Authors: Belonogova Nadezhda M. , Svishcheva Gulnara R. , Axenovich Tatiana I.
Published: March 2016

Summary: Several approaches to the region-based association analysis of quantitative traits have recently been developed and successively applied. However, no software package has been developed that implements all of these approaches for either independent or structured samples. Here we introduce FREGAT (Family REGional Association Tests), an R package that can handle family and population samples and implements a wide range of region-based association methods including burden tests, functional linear models, and kernel machine-based regression. FREGAT can be used in genome/exome-wide region-based association studies of quantitative traits and candidate gene analysis. FREGAT offers many useful options to empower its users and increase the effectiveness and applicability of region-based association analysis.

Availability and Implementation:  https://cran.r-project.org/web/packages/FREGAT/index.html

Supplementary Information:  Supplementary data are available at Bioinformatics Online.

Contact:  belon@bionet.nsc.ru
HilbertCurve: an R/Bioconductor package for high-resolution visualization of genomic data
Authors: Gu Zuguang , Eils Roland , Schlesner Matthias
Published: March 2016

Summary: Hilbert curves enable high-resolution visualization of genomic data on a chromosome- or genome-wide scale. Here we present the HilbertCurve package that provides an easy-to-use interface for mapping genomic data to Hilbert curves. The package transforms the curve as a virtual axis, thereby hiding the details of the curve construction from the user. HilbertCurve supports multiple-layer overlay that makes it a powerful tool to correlate the spatial distribution of multiple feature types.

Availability and implementation: The HilbertCurve package and documentation are freely available from the Bioconductor project: http://www.bioconductor.org/packages/devel/bioc/html/HilbertCurve.html

Contact:  m.schlesner@dkfz.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Canvas: versatile and scalable detection of copy number variants
Authors: Roller Eric , Ivakhno Sergii , Lee Steve , Royce Thomas , Tanner Stephen
Published: March 2016

Motivation: Versatile and efficient variant calling tools are needed to analyze large scale sequencing datasets. In particular, identification of copy number changes remains a challenging task due to their complexity, susceptibility to sequencing biases, variation in coverage data and dependence on genome-wide sample properties, such as tumor polyploidy or polyclonality in cancer samples.

Results: We have developed a new tool, Canvas, for identification of copy number changes from diverse sequencing experiments including whole-genome matched tumor-normal and single-sample normal re-sequencing, as well as whole-exome matched and unmatched tumor-normal studies. In addition to variant calling, Canvas infers genome-wide parameters such as cancer ploidy, purity and heterogeneity. It provides fast and easy-to-run workflows that can scale to thousands of samples and can be easily incorporated into variant calling pipelines.

Availability and Implementation: Canvas is distributed under an open source license and can be downloaded from https://github.com/Illumina/canvas.

Contact:  eroller@illumina.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Quantitative phosphoproteomics-based molecular network description for high-resolution kinase-substrate interactome analysis
Authors: Narushima Yuta , Kozuka-Hata Hiroko , Tsumoto Kouhei , Inoue Jun-Ichiro , Oyama Masaaki
Published: March 2016

Motivation: Phosphorylation-dependent cellular signaling is known to play a diverse role in regulating multiple cellular processes such as proliferation, differentiation and apoptosis. Recent technological advances in mass spectrometry-based phosphoproteomics have enabled us to measure network-wide signaling dynamics in a comprehensive and quantitative manner. As conventional protein–protein interaction (PPI) information-based network analysis is insufficient to systematically analyze phosphorylation site-dependent complex interaction dynamics, here we develop and evaluate a platform to provide a high-resolution molecular network description for kinase–substrate interactome analysis.

Results: In this study, we developed a Cytoscape-based bioinformatical platform named ‘Post Translational Modification mapper (PTMapper)’ to integrate PPI data with publicly available kinase-substrate relations at the resolution of phosphorylated amino acid residues. The previous phosphoproteome data on EGF-induced cellular signaling in glioblastoma stem cells was applied to evaluate our platform, leading to discovery of phosphorylation-dependent crucial signaling modulation in the p70S6K1-related pathway. Our study revealed that high-resolution cellular network description of phosphorylation-site dependent kinase-substrate signaling regulation should accelerate phosphoproteomics-based exploration of novel drug targets in the context of each disease-related signaling.

Availability and Implementation: PTMapper and the example data for construction of phosphorylation site-oriented networks are available at https://github.com/y-narushima/PTMapper.

Contact:  moyama@ims.u-tokyo.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
Deep models for brain EM image segmentation: novel insights and improved performance
Authors: Fakhry Ahmed , Peng Hanchuan , Ji Shuiwang
Published: March 2016

Motivation: Accurate segmentation of brain electron microscopy (EM) images is a critical step in dense circuit reconstruction. Although deep neural networks (DNNs) have been widely used in a number of applications in computer vision, most of these models that proved to be effective on image classification tasks cannot be applied directly to EM image segmentation, due to the different objectives of these tasks. As a result, it is desirable to develop an optimized architecture that uses the full power of DNNs and tailored specifically for EM image segmentation.

Results: In this work, we proposed a novel design of DNNs for this task. We trained a pixel classifier that operates on raw pixel intensities with no preprocessing to generate probability values for each pixel being a membrane or not. Although the use of neural networks in image segmentation is not completely new, we developed novel insights and model architectures that allow us to achieve superior performance on EM image segmentation tasks. Our submission based on these insights to the 2D EM Image Segmentation Challenge achieved the best performance consistently across all the three evaluation metrics. This challenge is still ongoing and the results in this paper are as of June 5, 2015.

Availability and Implementation: https://github.com/ahmed-fakhry/dive

Contact: sji@eecs.wsu.edu
Salmonella enterica Subspecies diarizonae Maxillary Sinusitis in a Snake Handler: First Report
Authors: Horvath Lukas , Kraft Marcel , Fostiropoulos Karolos , Falkowski Anna , Tarr Philip E.
Published: March 2016

In this study, we report the first case of reptile-associated maxillary sinusitis due to Salmonella enterica subspecies diarizonae in a snake handler and the third case of salmonella-associated sinusitis worldwide. The case highlights the potential of respiratory transmission and atypical salmonellosis presentations.
Pulsed Electromagnetic Fields for Postsurgical Pain Management in Women Undergoing Cesarean Section
Authors: Khooshideh Maryam , Latifi Rostami Seyedeh Sakineh , Sheikh Mahdi , Ghorbani Yekta Batool , Shahriari Ali
Published: March 2016

Objectives:

To evaluate the efficacy of pulsed electromagnetic field (PEMF) in relation to reducing postoperative pain, analgesic use, and wound healing in patients undergoing Cesarean section (C-section).

Methods:

This randomized, double-blind, placebo-controlled trial evaluated 72 women who underwent elective C-section. Thirty-six patients were assigned to the active-PEMF and 36 to the sham-PEMF groups. The participants were asked to report their pain intensity on a Visual Analog Scale (VAS) at 2, 4, 6, 12, and 24 hours and 2, 4, and 7 days after surgery. The amount of analgesics used was recorded. The surgical site was evaluated to assess the wound-healing process on the seventh postoperative day.

Results:

Postoperative pain VAS scores were significantly lower in the active-PEMF group in all the measured periods within the early and the late postoperative periods. Fewer women in the active-PEMF group experienced severe postoperative pain within 24 hours postoperatively (36% vs. 72%,P=0.002). Analgesic use during the first 24 hours after C-section was 1.9-times lower in the active-PEMF group (1.6±0.7 vs. 3.1±1.2,P<0.001). The total analgesic use during the seventh postoperative days was 2.1-times lower in the active-PEMF group than in the sham group (1.7±0.7 vs. 3.7±1.1,P<0.001). Seven days postoperatively, patients in the active-PEMF group had better wound healing with no exudate, erythema, or edema (P=0.02).

Conclusions:

PEMF treatment after C-section decreases postsurgical pain, analgesic use, and surgical wound exudate and edema significantly, and is associated with a high level of patient satisfaction.
Persistent Breast Pain Among Women With Histories of Breast-conserving Surgery for Breast Cancer Compared With Women Without Histories of Breast Surgery or Cancer
Authors: Edmond Sara N. , Shelby Rebecca A. , Keefe Francis J. , Fisher Hannah M. , Schmidt John E. , Soo Mary S. , Skinner Celette S. , Ahrendt Gretchen M. , Manculich Jessica , Sumkin Jules H. , Zuley Margarita L. , Bovbjerg Dana H.
Published: March 2016

Objectives:

This study compared persistent breast pain among women who received breast-conserving surgery for breast cancer and women without a history of breast cancer.

Methods:

Breast cancer survivors (n=200) were recruited at their first postsurgical surveillance mammogram (6 to 15 mo postsurgery). Women without a breast cancer history (n=150) were recruited at the time of a routine screening mammogram. All women completed measures of breast pain, pain interference with daily activities and intimacy, worry about breast pain, anxiety symptoms, and depression symptoms. Demographic and medical information were also collected.

Results:

Persistent breast pain (duration ≥6 mo) was reported by 46.5% of breast cancer survivors and 12.7% of women without a breast cancer history (P<0.05). Breast cancer survivors also had significantly higher rates of clinically significant persistent breast pain (pain intensity score ≥3/10), as well as higher average breast pain intensity and unpleasantness scores. Breast cancer survivors with persistent breast pain had significantly higher levels of depressive symptoms, as well as pain worry and interference, compared with survivors without persistent breast pain or women without a breast cancer history. Anxiety symptoms were significantly higher in breast cancer survivors with persistent breast pain compared with women without a breast cancer history.

Discussion:

Results indicate that persistent breast pain negatively impacts women with a history of breast-conserving cancer surgery compared with women without that history. Strategies to ameliorate persistent breast pain and to improve adjustment among women with persistent breast pain should be explored for incorporation into standard care for breast cancer survivors.
Differences in Clinical Pain and Experimental Pain Sensitivity Between Asian Americans and Whites With Knee Osteoarthritis
Authors: Ahn Hyochol , Weaver Michael , Lyon Debra E. , Kim Junglyun , Choi Eunyoung , Staud Roland , Fillingim Roger B.
Published: March 2016

Objective:

Ethnicity has been associated with clinical and experimental pain responses. Whereas ethnic disparities in pain in other minority groups compared with whites are well described, pain in Asian Americans remains poorly understood. The purpose of this study was to characterize differences in clinical pain intensity and experimental pain sensitivity among older Asian American and non-Hispanic white (NHW) participants with knee osteoarthritis (OA).

Methods:

Data were collected from 50 Asian Americans ages 45 to 85 (28 Korean, 9 Chinese, 7 Japanese, 5 Filipino, and 1 Indian) and compared with 50 age-matched and sex-matched NHW individuals with symptomatic knee OA pain. The Western Ontario and McMaster Universities Osteoarthritis Index and Graded Chronic Pain Scale were used to assess the intensity of clinical knee pain. In addition, quantitative sensory testing was used to measure experimental sensitivity to heat-induced and mechanically induced pain.

Results:

Asian American participants had significantly higher levels of clinical pain intensity than NHW participants with knee OA. In addition, Asian American participants had significantly higher experimental pain sensitivity than NHW participants with knee OA.

Discussion:

These findings add to the growing literature regarding ethnic and racial differences in clinical pain intensity and experimental pain sensitivity. Asian Americans in particular may be at risk for clinical pain and heightened experimental pain sensitivity. Further investigation is needed to identify the mechanisms underlying ethnic group differences in pain between Asian Americans and NHWs, and to ensure that ethnic group disparities in pain are ameliorated.
Mindfulness is Associated With Increased Hedonic Capacity Among Chronic Pain Patients Receiving Extended Opioid Pharmacotherapy
Authors: Thomas Elizabeth A. , Garland Eric L.
Published: March 2016

Objectives:

Chronic pain and long-term opioid use may lead to a persistent deficit in hedonic capacity, characterized by increased sensitivity to aversive states and insensitivity to natural rewards. Dispositional mindfulness has been linked with improved emotion regulation and pain coping. The aim of the current study was to examine associations between dispositional mindfulness, hedonic capacity, and pain-related interference in an opioid-using chronic pain sample.

Methods:

Data were obtained from a sample of 115 chronic pain patients on long-term opioid therapy (68% females, M age=48.3, SD=13.6) who completed the Five Facet Mindfulness Questionnaire (FFMQ), the Snaith-Hamilton Anhedonia and Pleasure Scale (SHAPS), the Brief Pain Inventory, and a psychiatric assessment of major depression. Bivariate correlations, hierarchical multiple regression, and path analysis were used to determine whether dispositional mindfulness scores (FFMQ) predicted variance in hedonic capacity (SHAPS), and whether hedonic capacity mediated the association between mindfulness and pain interference.

Results:

We observed a significant positive correlation between dispositional mindfulness and hedonic capacity scores (r=0.33, P<0.001). Hierarchical regression indicated that after controlling for pain interference and major depressive disorder diagnosis, dispositional mindfulness explained a significant portion of variance in hedonic capacity (β=0.30, P<0.01). The association between dispositional mindfulness and pain interference was mediated by hedonic capacity (b=−0.011, SE=0.005; 95% CI, −0.004 to −0.024, full model R
2=0.39).

Discussion:

Findings indicate that dispositional mindfulness was associated with hedonic capacity among this chronic pain sample. In light of this association, it is plausible that interventions that increase mindfulness may reduce pain-related impairment among opioid-using patients by enhancing hedonic capacity.
Prediction of Acute Postoperative Pain Following Breast Cancer Surgery Using the Pain Sensitivity Questionnaire
Authors: Rehberg Benno , Mathivon Stanislas , Combescure Christophe , Mercier Yannick , Savoldelli Georges L.
Published: March 2016

Objectives:

Previous studies have indicated that preoperative pain sensitivity correlates with postoperative pain intensity, and thus may be used to predict severe postoperative pain. Self-rating of pain sensitivity using the “Pain Sensitivity Questionnaire (PSQ)” may be an adjunct to these measures.

Methods:

We tested the predictive ability of the PSQ as well as experimental parameters of pain sensitivity and other known risk factors for acute pain in 198 patients scheduled for breast cancer surgery. A multivariable logistic regression model was created for the binary outcome “maximum pain >3 during the first 24 hours postoperatively.”

Results:

The PSQ score proved to be an independent risk factor for at least moderate pain during the first 24 hours after surgery. Univariate analysis yielded in addition younger age, type of surgery (mastectomy vs. breast-conserving surgery), axillary dissection, expected pain, and the anxiety scores of the State-Trait Anxiety Inventory, as well as the score of the Beck Depression Inventory as risk factors. Of the experimental parameters of pain sensitivity, only the pain intensity elicited by a hot water bath was a predictor of at least moderate postoperative pain. Multivariable analysis led to a parsimonious model including only PSQ, the State-Trait Anxiety Inventory state score with a cutoff of ≥30, age with a cutoff of <55, mastectomy (vs. breast-conserving surgery), and axillary dissection.

Discussion:

Results need to be validated in a larger cohort and for other types of surgery, but use of the simple PSQ may help to identify patients at risk of intense acute postoperative pain.
High-density EMG Reveals Novel Evidence of Altered Masseter Muscle Activity During Symmetrical and Asymmetrical Bilateral Jaw Clenching Tasks in People With Chronic Nonspecific Neck Pain
Authors: Testa Marco , Geri Tommaso , Gizzi Leonardo , Falla Deborah
Published: March 2016

Objectives:

To characterize the distribution of masseter muscle activity and force control during bilateral jaw clenching tasks in people with chronic nonspecific neck pain, without an associated temporomandibular disorder.

Methods:

Twelve volunteers with nonspecific neck pain and 12 age-matched and sex-matched healthy individuals participated. Submaximal symmetrical and asymmetrical bilateral jaw clenching was performed with and without visual feedback of force. Force performance was assessed with indices of accuracy (mean distance, offset error) and precision (standard deviation, coefficient of variation of force). High-density, 2-dimensional, surface electromyography (EMG) was recorded to characterize bilateral masseter muscle activity. The EMG root mean square was computed for each location of the electrode grid to form a map of the EMG amplitude distribution, and the location of the center of activity was measured.

Results:

The patient group showed a different distribution of masseter muscle activity compared with pain-free individuals during both symmetrical and asymmetrical bilateral jaw clenching. The position of the center of activity was positioned more cranial (P<0.001; right masseter only) and more anteriorly in the patient group (P<0.0001). In addition, the patients with chronic neck pain displayed higher levels of masseter muscle activation compared with the control participants regardless of the specific task performed (P<0.0001).

Discussion:

People with chronic neck pain display increased activation and altered distribution of masseter muscle activity during a jaw-clenching coordination task. These results provide a greater appreciation of how secondary orofacial pain or temporomandibular disorders may develop in people with neck pain.
Safety of immune checkpoint inhibitors in Chinese patients with melanoma
Authors: Wen Xizhi , Wang Yao , Ding Ya , Li Dandan , Li Jingjing , Guo Yiqun , Peng Ruiqing , Zhao Jingjing , Zhang Xing , Zhang Xiao-Shi
Published: March 2016

This study aimed to determine the tolerability of Chinese melanoma patients, particularly those with hepatitis B virus (HBV) infection, to immune checkpoint inhibitor therapy. Patients with metastatic melanoma who received anti-cytotoxic T lymphocyte-associated antigen-4 antibody (ipilimumab) or anti-programmed death 1 antibody (pembrolizumab) therapy at our hospital between August 2012 and July 2015 were retrospectively reviewed. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Twenty-three patients with advanced melanoma were included; nine and 10 patients received infusions of ipilimumab and pembrolizumab, respectively, whereas four patients received concurrent ipilimumab and pembrolizumab therapy. There was no cessation of treatment because of agent-related adverse events in any patient. Immune-related adverse events were observed in 44% (4/9), 60% (6/10), 100% (4/4), and 61% (14/23) of patients receiving ipilimumab, pembrolizumab, concomitant ipilimumab and pembrolizumab, and any treatment, respectively. The most frequent immune-related adverse events were endocrine disorders (39%, 9/23), liver function abnormalities (22%, 5/23), and dermatological events (17%, 4/23). There were no gastrointestinal reactions. Toxicities were usually mild and easily managed; only 13% (3/23) of patients had grade 3 adverse events and none experienced grade 4 events or treatment-related death. No additional toxicity nor severe hepatotoxicity was observed in 11 patients who had previous HBV infection. The recommended anti-cytotoxic T lymphocyte-associated antigen-4 and anti-programmed death 1 antibody doses were well tolerated by Chinese patients. Thus, immune checkpoint inhibitors appear to be effective and safe in metastatic melanoma patients, including those with pre-existing HBV infection.
Prediction of Fat-Free Mass in Kidney Transplant Recipients
Authors: Størset Elisabet , von Düring Marit Elizabeth , Godang Kristin , Bergan Stein , Midtvedt Karsten , Åsberg Anders
Published: March 2016

Background:

Individualization of drug doses is essential in kidney transplant recipients. For many drugs, the individual dose is better predicted when using fat-free mass (FFM) as a scaling factor. Multiple equations have been developed to predict FFM based on healthy subjects. These equations have not been evaluated in kidney transplant recipients. The objectives of this study were to develop a kidney transplant specific equation for FFM prediction and to evaluate its predictive performance compared with previously published equations.

Methods:

Ten weeks after transplantation, FFM was measured by dual-energy X-ray absorptiometry. Data from a consecutive cohort of 369 kidney transplant recipients were randomly assigned to an equation development data set (n = 245) or an evaluation data set (n = 124). Prediction equations were developed using linear and nonlinear regression analysis. The predictive performance of the developed equation and previously published equations in the evaluation data set was assessed.

Results:

The following equation was developed: FFM (kg) = {FFMmax × body weight (kg)/[81.3 + body weight (kg)]} × [1 + height (cm) × 0.052] × [1−age (years) × 0.0007], where FFMmax was estimated to be 11.4 in males and 10.2 in females. This equation provided an unbiased, precise prediction of FFM in the evaluation data set: mean error (ME) (95% CI), −0.71 kg (−1.60 to 0.19 kg) in males and −0.36 kg (−1.52 to 0.80 kg) in females, root mean squared error 4.21 kg (1.65–6.77 kg) in males and 3.49 kg (1.15–5.84 kg) in females. Using previously published equations, FFM was systematically overpredicted in kidney-transplanted males [ME +1.33 kg (0.40–2.25 kg) to +5.01 kg (4.06–5.95 kg)], but not in females [ME −2.99 kg (−4.07 to −1.90 kg) to +3.45 kg (2.29–4.61) kg].

Conclusions:

A new equation for FFM prediction in kidney transplant recipients has been developed. The equation may be used for population pharmacokinetic modeling and clinical dose selection in kidney transplant recipients.
Relieving pain using dose-extending placebos: a scoping review
Authors: Colloca Luana , Enck Paul , DeGrazia David
Published: March 2016

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22 studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Provided that nondisclosure is preauthorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated.
The musculoskeletal diagnosis cohort: examining pain and pain care among veterans
Authors: Goulet Joseph L. , Kerns Robert D. , Bair Matthew , Becker William C. , Brennan Penny , Burgess Diana J. , Carroll Constance M. , Dobscha Steven , Driscoll Mary A. , Fenton Brenda T. , Fraenkel Liana , Haskell Sally G. , Heapy Alicia A. , Higgins Diana M. , Hoff Rani A. , Hwang Ula , Justice Amy C. , Piette John D. , Sinnott Patsi , Wandner Laura , Womack Julie A. , Brandt Cynthia A.
Published: March 2016

Musculoskeletal disorders (MSDs) are highly prevalent, painful, and costly disorders. The MSD Cohort was created to characterize variation in pain, comorbidities, treatment, and outcomes among patients with MSD receiving Veterans Health Administration care across demographic groups, geographic regions, and facilities. We searched electronic health records to identify patients treated in Veterans Health Administration who had ICD-9-CM codes for diagnoses including, but not limited to, joint, back, and neck disorders, and osteoarthritis. Cohort inclusion criteria were 2 or more outpatient visits occurring within 18 months of one another or one inpatient visit with an MSD diagnosis between 2000 and 2011. The first diagnosis is the index date. Pain intensity numeric rating scale (NRS) scores, comorbid medical and mental health diagnoses, pain-related treatments, and other characteristics were collected retrospectively and prospectively. The cohort included 5,237,763 patients; their mean age was 59, 6% were women, 15% identified as black, and 18% reported severe pain (NRS ≥ 7) on the index date. Nontraumatic joint disorder (27%), back disorder (25%), and osteoarthritis (21%) were the most common MSD diagnoses. Patients entering the cohort in recent years had more concurrent MSD diagnoses and higher NRS scores. The MSD Cohort is a rich resource for collaborative pain-relevant health service research.
Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor: implications for migraine
Authors: Oliveira Margarida-Martins , Akerman Simon , Tavares Isaura , Goadsby Peter J.
Published: March 2016

Migraine is a painful neurologic disorder with premonitory symptomatology that can include disturbed appetite. Migraine pathophysiology involves abnormal activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is synthesized in the brain and is involved in pain modulation. NPY receptors are present in trigeminal ganglia and trigeminal nucleus caudalis suggesting a role in migraine pathophysiology. The present study aimed to determine the effect of systemic administration of NPY on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We performed in vivo electrophysiology in anesthetized rats, administered NPY (10, 30, and 100 µg·kg−1), and investigated the receptors involved by studying NPY Y1(30 µg·kg−1), Y2(30 µg·kg−1), and Y5receptor agonists (100·µg·kg−1), and NPY Y1receptor antagonist (30 µg·kg−1). NPY (30 and 100 µg·kg−1) significantly reduced TCC neuronal firing in response to dural-evoked trigeminovascular activation, but only NPY (30 µg·kg−1) significantly reduced spontaneous trigeminal firing. NPY Y1receptor agonist also significantly reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 µg·kg−1), NPY Y2, and Y5receptor agonists, and the NPY Y1receptor antagonist had no significant effects on nociceptive dural-evoked neuronal firing in the TCC or spontaneous trigeminal firing. This study demonstrates that NPY dose dependently inhibits dural-evoked trigeminal activity, through NPY Y1receptor activation, indicating antinociceptive actions of NPY in a migraine animal model. Based on the role of NPY in appetite regulation, it is possible that disruption of the NPY system might explain changes of appetite in migraineurs.
Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis
Authors: Ditre Joseph W. , Heckman Bryan W. , Zale Emily L. , Kosiba Jesse D. , Maisto Stephen A.
Published: March 2016

Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.
Pediatric Brain Tumors: Current Knowledge and Therapeutic Opportunities
Authors: Glod John , Rahme Gilbert J. , Kaur Harpreet , H. Raabe Eric , Hwang Eugene I. , Israel Mark A.
Published: March 2016

Great progress has been made in many areas of pediatric oncology. However, tumors of the central nervous system (CNS) remain a significant challenge. A recent explosion of data has led to an opportunity to understand better the molecular basis of these diseases and is already providing a foundation for the pursuit of rationally chosen therapeutics targeting relevant molecular pathways. The molecular biology of pediatric brain tumors is shifting from a singular focus on basic scientific discovery to a platform upon which insights are being translated into therapies.
Osteosarcoma With Apparent Ewing Sarcoma Gene Rearrangement
Authors: Mathias Melissa D. , Chou Alexander J. , Meyers Paul , Shukla Neerav , Hameed Meera , Agaram Narasimhan , Wang Lu , Berger Michael F. , Walsh Michael , Kentsis Alex
Published: March 2016

Poorly differentiated round cell sarcomas present diagnostic challenges because of their variable morphology and lack of specific immunophenotypic markers. We present a case of a 15-year-old female with a tibial tumor that exhibited features of Ewing-like sarcoma, including apparent rearrangement of the EWSR1 gene. Hybridization capture-based next-generation DNA sequencing showed evidence of complex genomic rearrangements, absence of known pathogenic Ewing-like chromosome translocations, and deletions RB1, PTCH1, and ATRX, supporting the diagnosis of osteosarcoma. This illustrates the potential of clinical genomic profiling to improve diagnosis and enable specifically targeted therapies for cancers with complex pathologies.
Cerebral Metastasis of Hepatoblastoma: A Review
Authors: Rai Parul , H. Feusner James
Published: March 2016

Hepatoblastoma is rarely reported to metastasize to the brain. A comprehensive review of the literature was undertaken to characterize such patients and to examine the various therapies utilized to treat them. We identified 39 patients, including 1 previously unreported case from our institution. Although only 19 of these patients had much demographic information reported, it is notable that 24% (4/17) were older than 4 years at their original primary tumor diagnosis and 63% (7/11) had evidence of pulmonary metastases (at original diagnosis or recurrence) before the occurrence of brain metastasis. On the basis of the limited data published about this rare presentation and the known association of poor outcome with older age at diagnosis, we recommend additional neuroimaging in older hepatoblastoma patients when they present for evaluation of a pulmonary recurrence even when they are neurologically asymptomatic, with the aim of early identification and surgical resection of these lesions. The role of radiotherapy as an adjunct treatment for multiple cerebral lesions looks promising and needs to be explored further.