bluuebunny/crossref_metadata_2025 huggingface dataset:
Ali Shariati: The Architect of the 1979 Islamic Revolution of Iran
Authors: Abedi Mehbi
Published: June 2018

Ali Shariati was born in Azar 2, 1312 (November 23, 1933) to a deeply religious family in the provincial capital of Khurasan, Meshed. His forefathers were all important local religious scholars in the suburb of Sabzavar, one of whom, Allamah Mahmanabadi, received a royal invitation from Naser al-din (1848-1896) to move to Tehran to teach Islamic philosophy in Sepahsalar theological center, which he did for a short period. His father, Muhammad Taqi Shariati, still living, is a well-known religious scholar of national fame and an expert on Quranic exegesis. Muhammad Taqi broke two traditions: he moved to the city for good at the age of 20 and he stopped weaving, as he had been the traditional garb of the ulama. Ali attended modern schools, entered Teachers Training College, the newly founded University of Meshed, and finally left for Paris to study at the Sorbonne on a government scholarship.
Prediction of human-Bacillus anthracis protein–protein interactions using multi-layer neural network
Authors: Ahmed Ibrahim , Witbooi Peter , Christoffels Alan
Published: June 2018

Motivation

Triplet amino acids have successfully been included in feature selection to predict human-HPV protein-protein interactions (PPI). The utility of supervised learning methods is curtailed due to experimental data not being available in sufficient quantities. Improvements in machine learning techniques and features selection will enhance the study of PPI between host and pathogen.

Results

We present a comparison of a neural network model versus SVM for prediction of host-pathogen PPI based on a combination of features including: amino acid quadruplets, pairwise sequence similarity, and human interactome properties. The neural network and SVM were implemented using Python Sklearn library. The neural network model using quadruplet features and other network features outperformance the SVM model. The models are tested against published predictors and then applied to the human-B.anthracis case. Gene ontology term enrichment analysis identifies immunology response and regulation as functions of interacting proteins. For prediction of Human-viral PPI, our model (neural network) is a significant improvement in overall performance compared to a predictor using the triplets feature and achieves a good accuracy in predicting human-B.anthracis PPI.

Availability and implementation

All code can be downloaded from ftp://ftp.sanbi.ac.za/machine_learning/.

Supplementary information

Supplementary data are available at Bioinformatics online.
ncdDetect2: improved models of the site-specific mutation rate in cancer and driver detection with robust significance evaluation
Authors: Juul Malene , Madsen Tobias , Guo Qianyun , Bertl Johanna , Hobolth Asger , Kellis Manolis , Pedersen Jakob Skou
Published: June 2018

Motivation

Understanding the mutational processes that act during cancer development is a key topic of cancer biology. Nevertheless, much remains to be learned, as a complex interplay of processes with dependencies on a range of genomic features creates highly heterogeneous cancer genomes. Accurate driver detection relies on unbiased models of the mutation rate that also capture rate variation from uncharacterized sources.

Results

Here, we analyse patterns of observed-to-expected mutation counts across 505 whole cancer genomes, and find that genomic features missing from our mutation-rate model likely operate on a megabase length scale. We extend our site-specific model of the mutation rate to include the additional variance from these sources, which leads to robust significance evaluation of candidate cancer drivers. We thus present ncdDetect v.2, with greatly improved cancer driver detection specificity. Finally, we show that ranking candidates by their posterior mean value of their effect sizes offers an equivalent and more computationally efficient alternative to ranking by their P-values.

Availability and implementation

ncdDetect v.2 is implemented as an R-package and is freely available at http://github.com/TobiasMadsen/ncdDetect2

Supplementary information

Supplementary data are available at Bioinformatics online.
Prefrontal Control Over Occipital Responses to Crossmodal Overlap Varies Across the Congruency Spectrum
Authors: Lundström Johan N , Regenbogen Christina , Ohla Kathrin , Seubert Janina
Published: June 2018

While matched crossmodal information is known to facilitate object recognition, it is unclear how our perceptual systems encode the more gradual congruency variations that occur in our natural environment. Combining visual objects with odor mixtures to create a gradual increase in semantic object overlap, we demonstrate high behavioral acuity to linear variations of olfactory–visual overlap in a healthy adult population. This effect was paralleled by a linear increase in cortical activation at the intersection of occipital fusiform and lingual gyri, indicating linear encoding of crossmodal semantic overlap in visual object recognition networks. Effective connectivity analyses revealed that this integration of olfactory and visual information was achieved by direct information exchange between olfactory and visual areas. In addition, a parallel pathway through the superior frontal gyrus was increasingly recruited towards the most ambiguous stimuli. These findings demonstrate that cortical structures involved in object formation are inherently crossmodal and encode sensory overlap in a linear manner. The results further demonstrate that prefrontal control of these processes is likely required for ambiguous stimulus combinations, a fact of high ecological relevance that may be inappropriately captured by common task designs juxtaposing congruency and incongruency.
The L2 Weak Sequential Convergence of Radial Focusing Mass Critical NLS Solutions with Mass Above the Ground State
Authors: Fan Chenjie
Published: June 2018

We study the non-scattering $L^{2}$ solution $u$ to the radial focusing mass-critical nonlinear Schrödinger equation with mass just above the ground state, and show that there exists a time sequence $\{t_{n}\}_{n}$, such that $u(t_{n})$ weakly converges to the ground state $Q$ up to scaling and phase transformation. We also give some partial results on the mass concentration phenomena of the minimal mass blow-up solution.
Local Models of Isolated Singularities for Affine Special Kähler Structures in Dimension Two
Authors: Callies Martin , Haydys Andriy
Published: June 2018

We construct local models of isolated singularities for special Kähler structures in real dimension two assuming that the associated holomorphic cubic form does not have essential singularities. As an application we compute the holonomy of the flat symplectic connection, which is a part of the special Kähler structure.
Who Leaves Early? Factors Associated With Against Medical Advice Discharge During Alcohol Withdrawal Treatment
Authors: Pytell Jarratt D. , Rastegar Darius A.
Published: June 2018

Objective:

To determine if certain patient, clinical, and disease factors are associated with against medical advice (AMA) discharge among patients admitted for treatment of alcohol withdrawal.

Methods:

Data from admissions to a dedicated unit for treatment of substance withdrawal were collected over a 6-month period. Patients with AMA and planned discharge were compared with regard to demographics, clinical data, and substance use disorder disease characteristics. A stepwise logistic regression was used to find the best model.

Results:

The study population included 655 patient encounters. A total of 93 (14%) discharges were AMA. Bivariate analysis showed patients with AMA discharge were younger (mean age 43 vs 46 years; P < 0.05), more likely to leave on a Tuesday to Thursday, and to have an initial withdrawal score at or above the median (AMA 69% vs planned 56%; P = 0.02). Emergency department (ED) admissions had an AMA discharge rate of 21% compared with 10% of community admissions (P < 0.05). Regression analysis found AMA discharge was significantly associated with admission from the ED (odds ratio [OR] 2.03, confidence interval [CI] 1.27–3.25) and younger age (OR 0.97, CI 0.95–0.99). There was no significant difference in discharge disposition among patients with concurrent opioid use disorder who were on opioid agonist therapy.

Conclusions:

AMA discharges occurred in 1 of every 7 admissions. Being admitted from the ED and younger age was associated with AMA discharge. No other patient or clinical factors were found to be associated with AMA discharge.
Predictors of Leaving an Inpatient Medical Withdrawal Service Against Medical Advice: A Retrospective Analysis
Authors: Ling Sara , Cleverley Kristin , Brennenstuhl Sarah , Bindseil Kirstin
Published: June 2018

Objectives:

The purpose of this study was to determine the frequency and predictors of patients leaving an inpatient medical withdrawal unit against medical advice (AMA).

Methods:

This study used a case-control design to compare patients who were discharged AMA (n = 164) with those who completed treatment (n = 678). Logistic regression analysis was used to determine which variables were independent predictors of patients leaving AMA.

Results:

We found that being admitted through the emergency department (odds ratio [OR] 3.17, confidence interval [CI] 1.66–6.08), having gamma-hydroxybutyrate (OR 7.61, CI 1.81–32.09) as a primary substance of concern compared to alcohol, and having multiple axis I psychiatric diagnoses (OR 2.20, CI 1.16–4.18) or depression (OR 2.86, CI 1.32–6.17) compared with no psychiatric diagnosis increased the odds of leaving inpatient medical withdrawal AMA. By contrast, not being dependent on nicotine (OR 0.45, CI 0.23–0.88) and increasing time since admission (OR 0.42, CI 0.36–0.48) reduced the odds of leaving AMA.

Conclusions:

The findings of this study reveal novel information about patients who leave inpatient medical withdrawal AMA and can inform targeted interventions to prevent vulnerable patients from terminating treatment early and improve healthcare service utilization.
Patients With Substance Use Disorders Leaving Against Medical Advice: Strategies for Improvement
Authors: Lail Parabhdeep , Fairbairn Nadia
Published: June 2018

In this issue of the Journal of Addiction Medicine, 2 studies fill an important gap in knowledge by examining predictors of leaving against medical advice from inpatient withdrawal management settings. The studies identify important risk factors for leaving against medical advice and highlight important areas for inpatient withdrawal management. These include the use of substance specific standardized protocols and initiation of opioid agonist treatment instead of opioid detoxification given harms associated with opioid withdrawal. Further need for increased training in addiction medicine for primary care physicians, and use of inpatient addiction medicine consult services as part of early intervention for substance withdrawal are also discussed.
Do Personality Factors Assessed Before Cochlear Implantation Predict Hearing-Related Quality Of Life After Cochlear Implantation in Postlingually Deafened Adults?
Authors: Muigg Franz , Bliem Harald R. , Holzner Bernhard , Kühn Heike , Zorowka Patrick G. , Weichbold Viktor W.
Published: June 2018

Background:

Studies have shown that cochlear implants improve deaf patients’ hearing-related quality of life (hrQoL), but the degree of improvement varies considerably between patients. This study investigated whether personality factors contribute to hrQoL outcome after cochlear implantation.

Method:

Fifty adult patients with postlingual hearing loss who received a unilateral cochlear implant were administered the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI; a personality inventory) and the Nijmegen Cochlear Implant Questionnaire (NCIQ; a hrQoL questionnaire). The NEO-FFI was administered only before implantation; the NCIQ was administered before implantation and 12 months after implant activation. A linear regression analysis was computed to detect whether NCIQ scores at 12 months were predicted by the NEO-FFI personality factors (i.e., Extraversion, Neuroticism, Openness to Experience, Agreeableness, and Conscientiousness) assessed before implantation.

Results:

HrQoL scores had significantly improved 12 months after cochlear implantation in all subdomains of the NCIQ. Of the five personality factors, solely Neuroticism was negatively associated to the NCIQ subdomain self-esteem (β = −0.34; p = 0.013) at 12 months after cochlear implantation.

Conclusions:

While significant improvement of hrQoL was seen 12 months after implant activation, this improvement was barely predicted by the Big-Five personality traits measured before implantation. Only Neuroticism was found to moderately influence postimplantation hrQoL in our patients, in the way that higher degrees of Neuroticism tend to go along with lower degrees of self-esteem (as conceptualized by the NCIQ). The failure to detect personality effects on hrQoL could partly be due to the low levels of Extraversion and Openness to Experience observed in our sample of patients with hearing loss.
Comparison of Two Posterior Three-Point Fixation Techniques for Treating Reducible Atlantoaxial Dislocation
Authors: Zhao Wenlong , Wu Yaming , Hu Wei , Ni Bin , Guo Qunfeng , Chen Jinshui , Guo Xiang
Published: June 2018

Study Design.

Retrospective comparative study.

Objective.

To compare the outcomes of C1–C2 transarticular screw combined with C1 laminar hook (TAS+C1H) and C1–C2 transarticular screw combined with modified Gallie technique (TAS+G) for treating reducible atlantoaxial dislocation (AAD).

Summary of Background Data.

Both TAS+C1H and TAS+G fixation were 3-point fixation techniques for AAD. TAS+C1H technique was comparable to TAS+G technique in biomechanics. However, it is unknown whether it can achieve same outcomes as TAS+G technique.

Methods.

Data of the 63 patients who underwent TAS+C1H or TAS+G fixation and fusion because of AAD were retrospectively reviewed. Bone fusion time was recorded. The outcomes evaluated by visual analog scale score for neck pain (VASSNP), Nurick scale, neck stiffness (none/mild/severe), patient satisfaction, and Neck Disability Index (NDI) were compared between two groups.

Results.

At the final follow-up, bone graft fusion rates were 100% in both groups (P > 0.05). Nurick scales were significantly improved in both groups (P < 0.05), but with no significant differences between groups (P > 0.05). There were no significant differences between two groups in VASSNP, neck stiffness, patient satisfaction, or NDI (all P > 0.05). There were no complications related to the surgical approach and instrumentation in either group.

Conclusion.

Both TAS+C1H and TAS+G fixation were effective in the treatment of reducible AAD. TAS+C1H was safer than TAS+G because it could potentially reduce the risk of spinal cord and venous plexus injury associated with sublaminar cables.

Level of Evidence: 3
Comparison of Postoperative Outcomes Between Primary MIS TLIF and MIS TLIF With Revision Decompression
Authors: Khechen Benjamin , Haws Brittany E. , Patel Dil V. , Narain Ankur S. , Hijji Fady Y. , Guntin Jordan A. , Cardinal Kaitlyn L. , Iyer Sravisht , Singh Kern
Published: June 2018

Study Design.

Retrospective cohort.

Objective.

To compare postoperative improvements in surgical and patient-reported outcomes (PROs) between patients undergoing minimally invasive laminectomy and minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) as a primary procedure to patients undergoing MIS laminectomy and TLIF as a revision to primary lumbar decompression (LD).

Summary of Background Data.

MIS TLIF and LD have demonstrated to be effective surgical options for lumbar degenerative disease. However, some patients undergoing LD experience recurrent symptoms and eventually require a revision decompression with fusion.

Methods.

A prospectively maintained surgical database of patients who underwent a primary or revision one-level MIS TLIF for degenerative spinal pathology between 2014 and 2016 was reviewed. Consecutive patients undergoing primary MIS TLIF and revision lumbar discectomy and/or laminectomy were matched in a one-to-one fashion to primary MIS TLIF patients who had not undergone a previous LD by age and preoperative diagnosis. Differences in patient demographic, comorbidity, and perioperative characteristics between procedure groups were assessed using Pearson chi-squared analysis and Student t test for categorical and continuous variables, respectively. Improvements in PROs from preoperative values were compared between primary and revision cohorts using Student t tests. Pearson chi-squared analysis was used to compare rates of minimum clinically important difference achievement between procedure groups. Statistical significant was set at P < 0.05.

Results.

A total of 52 patients were included in this analysis. Twenty-six underwent primary MIS laminectomy and TLIF and 26 underwent MIS TLIF with a revision decompression. No differences in baseline or perioperative variables were observed. Revision and primary MIS TLIF patients experienced similar improvements in PROs at all postoperative time points.

Conclusion.

The results of the present study demonstrate patients undergoing primary MIS TLIF with LD as a revision to a primary decompression experienced similar postoperative improvements in PROs as compared to primary MIS TLIF patients. This indicates a primary decompression does not compromise clinical outcomes in patients undergoing MIS TLIF. As such, patients should not be precluded from undergoing MIS TLIF based on the history of a previous LD.

Level of Evidence: 3
Three Methods of Pelvic Fixation for Scoliosis in Children With Cerebral Palsy
Authors: Abousamra Oussama , Sullivan Brian T. , Samdani Amer F. , Yaszay Burt , Cahill Patrick J. , Newton Peter O. , Sponseller Paul D.
Published: June 2018

Study Design.

A retrospective review.

Objective.

The aim of this study was to assess correction of pelvic obliquity in children with cerebral palsy (CP) scoliosis postoperatively and 5 years after posterior spinal fusion with pelvic fixation using unit rods, sacral-alar-iliac (SAI) screws, or iliac screws.

Summary of Background Data.

There are multiple options for pelvic fixation in children with scoliosis secondary to CP. The long-term differences in outcomes between these fixation methods are still unclear.

Methods.

A multicenter review identified records of 70 children with CP who underwent posterior spinal fusion for scoliosis using unit rods (n = 9), SAI screws (n = 19), or iliac screws (n = 42). Patients younger than 18 years with 5-year follow-up were included. Pelvic obliquity and major coronal curve measurements were compared using preoperative, (first erect) postoperative, and 5-year follow-up radiographs. Implant-related complications were noted. Alpha = 0.05.

Results.

For all groups, there was a significant difference between preoperative and postoperative pelvic obliquity that was maintained at 5 years. At 5-year follow-up, pelvic obliquity was significantly higher in the IS group (12°) compared with the unit rod group (4°, P = 0.001) and SAI screw group (6°) (P = 0.006). Implant-related complications were as follows: unit rod group, one patient (reoperation); SAI screw group, none; iliac screw group, six patients, including three cases of loss of connection between the rod and the iliac screw, two prominent screws, and one loose screw.

Conclusion.

Correction of pelvic obliquity for children with CP-related scoliosis was achieved postoperatively using unit rods, SAI screws, and iliac screws. Implant-related complications and reoperations were most common in the iliac screw group. At 5-year follow-up, the iliac screw group had loss of major curve correction and less correction of pelvic obliquity than the unit rod and SAI screw groups.

Level of Evidence: 3
Fragility Fracture Risk in Elderly Patients With Cervical Myelopathy
Authors: Horowitz Jason A. , Puvanesarajah Varun , Jain Amit , Raad Micheal , Gjolaj Joseph P. , Shen Francis H. , Hassanzadeh Hamid
Published: June 2018

Study Design.

Retrospective review.

Objective.

To identify and compare the incidences of fragility fractures amongst three elderly populations: the general population, patients with surgically treated cervical spondylotic myelopathy (CSM), and patients with CSM not surgically treated.

Summary of Background Data.

CSM is a common disease in the elderly. Progression of myelopathic symptoms, including gait imbalance, can be a source of morbidity as it can lead to increased falls.

Methods.

Records of elderly patients with Medicare insurance from 2005 to 2014 were retrospectively reviewed. Three mutually exclusive populations of patients were identified for analysis, including a cohort of patients with a diagnosis of CSM who were not treated with surgery; a cohort of patients with CSM who were treated with surgery; and a group of control patients who had never been treated with cervical spine surgery nor were diagnosed with CSM. Incidence of fractures of the distal radius, proximal humerus, proximal femur, and lumbar spine were assessed and compared between cohorts, adjusted by age, sex, osteoporosis, dementia, cerebrovascular disease, and Charlson Comorbidity Index.

Results.

A total of 891,864 patients were identified, of which 60,332 had a diagnosis of CSM and 24,439 underwent cervical spine surgery. Compared to general population controls, the 12-month adjusted odds of experiencing at least one fragility fracture were 1.59 times higher in patients with CSM who were not treated with surgery (P < 0.001). The analogous odds ratio was 1.34 (P < 0.001) at 3 years. Compared to nonsurgically treated patients with CSM, the odds of experiencing at least one fragility fracture were reduced to 0.89 in surgically treated patients (P = 0.008).

Conclusion.

Fragility fractures are a significant source of morbidity and mortality in elderly patients. CSM is associated with increased rates of fragility fractures, although surgical management of CSM may be protective against risk of fragility fracture.

Level of Evidence: 3
Management of the Critically Ill Adult Chimeric Antigen Receptor-T Cell Therapy Patient: A Critical Care Perspective
Authors: Gutierrez Cristina , McEvoy Colleen , Mead Elena , Stephens R. Scott , Munshi Laveena , Detsky Michael E. , Pastores Stephen M. , Nates Joseph L.
Published: June 2018

Objectives:

Chimeric antigen receptor T-cell therapy, a type of immune effector therapy for cancer, has demonstrated encouraging results in clinical trials for the treatment of patients with refractory hematologic malignancies. Nevertheless, there are toxicities specific to these treatments that, if not recognized and treated appropriately, can lead to multiple organ failure and death. This article is a comprehensive review of the available literature and provides, from a critical care perspective, recommendations by experienced intensivists in the care of critically ill adult chimeric antigen receptor T-cell patients.

Data Sources:

PubMed and Medline search of articles published from 2006 to date.

Study Selection:

Clinical studies, reviews, or guidelines were selected and reviewed by the authors.

Data Extraction:

Not available.

Data Synthesis:

Not available.

Conclusions:

Until modifications in chimeric antigen receptor T-cell therapy decrease their toxicities, the intensivist will play a leading role in the management of critically ill chimeric antigen receptor T-cell patients. As this novel immunotherapeutic approach becomes widely available, all critical care clinicians need to be familiar with the recognition and management of complications associated with this treatment.
Bempedoic Acid (ETC-1002): ATP Citrate Lyase Inhibitor
Authors: Zagelbaum Nicole K. , Yandrapalli Srikanth , Nabors Christopher , Frishman William H.
Published: June 2018

Bempedoic acid (BA; ETC-1002) is a new agent that reduces cholesterol synthesis through inhibition of adenosine triphosphate citrate lyase, an enzyme upstream from 3-hydroxy-3-methylglutaryl-coenzyme A. In animal models, BA also influences fatty acid synthesis, but in humans, its role is limited primarily to lowering low-density lipoprotein cholesterol (LDL-C). In early clinical trials, BA was well tolerated and without major side effects. Alone or in various combinations with atorvastatin and/or ezetimibe, LDL-C lowering ranged from 17% to 64%. In addition, BA lowers levels of non–high-density lipoprotein cholesterol, C-reactive protein, and apolipoprotein B. Statins are first-line agents for primary and secondary prevention of cardiovascular disease. However, muscle-related side effects and other problems such as elevated liver enzymes may limit their use. In addition, LDL-C lowering beyond that provided by statin therapy alone may be needed. BA may be useful in either of these scenarios, as it is relatively free of muscle-related side effects and appears to enhance LDL-C lowering beyond that achieved with statin monotherapy. Phase 3 trials and one outcomes study are currently under way to better define this agent’s potential clinical role.
Functional Mitral Regurgitation
Authors: Van Assche Lowie M. R. , Ricciardi Mark J.
Published: June 2018

Functional mitral regurgitation (FMR) is common in patients with heart failure and portends a poor prognosis. The etiology is secondary to nonischemic or ischemic (postmyocardial infarction) adverse remodeling. Treatment includes guideline-directed medical therapy, cardiac resynchronization therapy, and in some cases, surgical repair or replacement. Transcatheter mitral valve (MV) repair with the MitraClip device is approved in patients with degenerative MR and is currently under investigation for use in FMR, as are several transcatheter MV replacement devices. This review discusses the basis of FMR pathophysiology, classification, and prognosis; provides an overview of current therapeutic approaches; examines the available literature on the use of MitraClip in patients with FMR; and provides insight into ongoing clinical trials and new investigational devices for the treatment of FMR.
Experiences of Population Monitoring Using Whole-Body Counters in Response to the Fukushima Nuclear Accident
Authors: Kurihara Osamu , Li Chunsheng , Lopez Maria Antonia , Kim Eunjoo , Tani Kotaro , Nakano Takashi , Takada Chie , Momose Takumaro , Akashi Makoto
Published: June 2018

Whole-body counter measurements of residents of Fukushima Prefecture have been extensively performed after the Fukushima Dai-ichi Nuclear Power Plant accident in March 2011. These measurements have demonstrated that the levels of internal contamination with radioactive cesium (134Cs and 137Cs) in the residents are very low. This article provides an overview of and lessons learned from these whole-body counter measurements with emphasis on the technical problems encountered, and it discusses the effective use of whole-body counters for assessing the internal thyroid doses of individuals when direct measurements of 131I in the thyroid are difficult or impossible to implement for the total affected population in a short time after a nuclear reactor accident. The application of this dose reconstruction method requires determining the intake ratio of 131I to cesium isotopes at appropriate times and considers the short biological half-lives of cesium isotopes, in particular for children.
Efficacy of hypnosis on pain, wound-healing, anxiety, and stress in children with acute burn injuries: a randomized controlled trial
Authors: Chester Stephen J. , Tyack Zephanie , De Young Alexandra , Kipping Belinda , Griffin Bronwyn , Stockton Kellie , Ware Robert S. , Zhang Xi , Kimble Roy M.
Published: June 2018

No randomized controlled trial has investigated the efficacy of hypnosis for reducing pain and improving wound-healing in children with burns. This randomized controlled trial aimed to investigate whether hypnosis decreases pain, anxiety, and stress and accelerates wound-healing in children undergoing burn wound procedures. Children (4-16 years) with acute burns presenting for their first dressing change were randomly assigned to a Hypnosis Group who received hypnosis plus standard care or a Standard Care Group who received standard pharmacological and nonpharmacological intervention. Repeated measures of pain intensity, anxiety, stress, and wound-healing were taken at dressing changes until ≥95% wound re-epithelialization. Data for 62 children were analyzed on an intent-to-treat basis using Generalized Estimating Equations (n = 35 Standard Care Group; n = 27 Hypnosis Group). An effect on the primary outcomes of pain and wound healing was not supported {self-reported pain intensity largest Mean Difference [MD] = −0.85 (95% confidence interval [CI]: −1.91 to 0.22), P = 0.12; MD for re-epithelialization = −0.46 [95% CI: −4.27 to 3.35], P = 0.81}. Some support was found for an effect on the secondary outcomes of preprocedural anxiety (MD = −0.80 [95% CI: −1.50 to −0.10], P = 0.03 before the second dressing change) and heart rate as a measure of stress (MD = −15.20 [−27.20 to −3.20], P = 0.01 and MD = −15.39 [−28.25 to −2.53], P = 0.02 before and after the third dressing change). Hypnosis may be effective for decreasing preprocedural anxiety and heart rate in children undergoing repeated pediatric wound care procedures but not for reducing pain intensity or accelerating wound healing.
Involvement of lysophosphatidic acid–induced astrocyte activation underlying the maintenance of partial sciatic nerve injury–induced neuropathic pain
Authors: Ueda Hiroshi , Neyama Hiroyuki , Nagai Jun , Matsushita Yosuke , Tsukahara Tamotsu , Tsukahara Ryoko
Published: June 2018

We have previously demonstrated that lysophosphatidic acid (LPA) plays key roles in the initial mechanisms for neuropathic pain (NeuP) development. Here, we examined whether LPA receptor mechanisms and LPA production are related to the glial activation at a late stage after partial sciatic nerve ligation (pSNL) by use of microglial inhibitor, Mac1-saporin or astrocyte inhibitor, and l-α-aminoadipate (l-AA). Although single intrathecal injection of LPA1/3 antagonist, Ki-16425 did not affect the pain threshold at day 7 after the spinal cord injury, repeated treatments of each compound gradually reversed the basal pain threshold to the control level. The intrathecal administration of a microglia inhibitor, Mac-1-saporin reversed the late hyperalgesia and LPA production at day 14 after the pSNL, whereas l-AA inhibited the hyperalgesia, but had no effect on LPA production. The involvement of LPA receptors in astrocyte activation in vivo was evidenced by the findings that Ki-16425 treatments abolished the upregulation of CXCL1 in activated astrocytes in the spinal dorsal horn of mice at day 14 after the pSNL, and that Ki-16425 reversed the LPA-induced upregulation of several chemokine gene expressions in primary cultured astrocytes. Finally, we found that significant hyperalgesia was observed with intrathecal administration of primary cultured astrocytes, which had been stimulated by LPA in a Ki-16425–reversible manner. All these findings suggest that LPA production and LPA1/3 receptor activation through differential glial mechanisms play key roles in the maintenance as well as initiation mechanisms in NeuP.
Location-specific responses to nociceptive input support the purposeful nature of motor adaptation to pain
Authors: Gallina Alessio , Salomoni Sauro E. , Hall Leanne M. , Tucker Kylie , Garland S. Jayne , Hodges Paul W.
Published: June 2018

Movement is changed in pain, but the mechanisms remain unclear. Key questions are unresolved such as whether activation can be inhomogeneously distributed within a muscle in a manner that is specific to the location of noxious input. This study addressed this question using high-density electromyography (EMG) to study regional redistribution of muscle activation within the vasti muscles and changes in knee extension force direction in response to noxious stimulation applied to muscular and nonmuscular tissues around the knee. Fourteen participants performed a low-force knee extension contraction at baseline, during, and after pain induced in 4 locations (infrapatellar fat pad, vastus lateralis, distal vastus medialis, or proximal vastus medialis). The knee extension force direction was estimated from a 3-dimensional load cell positioned just above the ankle. Regional muscle activation was estimated from amplitude of high-density surface EMG signals from vastus medialis and lateralis. Pain-induced spatial variations of activation were identified as the position of the 5 channels that showed the largest decrease (or smallest increase) in amplitude from baseline to pain or after pain. Knee extension force was produced more medially during pain after infrapatellar pad injection only (P = 0.01). Preferential reduction of activation of the distal region of vastus medialis was observed when distal vastus medialis (P < 0.001) or vastus lateralis (P < 0.05) was injected. Both adaptations persisted after pain resolution. These results support the hypothesis that specific adaptation depends on the location of a noxious stimulus and imply that recovery of pain is not necessarily concomitant with return of the EMG to prepain patterns.
Influence of neuropathic pain on nicotinic acetylcholine receptor plasticity and behavioral responses to nicotine in rats
Authors: Brunori Gloria , Schoch Jennifer , Mercatelli Daniela , Ozawa Akihiko , Toll Lawrence , Cippitelli Andrea
Published: June 2018

Tobacco smoking is particularly evident in individuals experiencing chronic pain. This complex relationship is poorly understood at both molecular and behavioral levels. Here, we describe experiments aimed at understanding whether a chronic pain state induces neuroadaptations into the brain or peripheral nerves that involve nicotinic acetylcholine receptors (nAChRs) and whether these neuroadaptations directly lead to increased vulnerability to nicotine addiction or to the development of coping strategies to relieve pain symptoms. We found that ligation of the rat L5 spinal nerve led to a dramatic downregulation in the mRNA expression levels of all nAChR subunits examined in dorsal root ganglia and a time-dependent downregulation of discrete subunits, particularly in the cingulate cortex and the amygdala. Spinal nerve ligation and sham-operated rats showed minor or no changes in patterns of acquisition and motivation for nicotine taking. Spinal nerve ligation rats also showed similar vulnerability to nicotine seeking as sham animals when reinstatement was induced by nicotine-associated cues, but failed to reinstate lever pressing when relapse was induced by nicotine priming. Spinal nerve ligation and sham rats were equally sensitive to nicotine-induced anxiety-like behavior and antinociception; however, nicotine produced a potent and long-lasting antiallodynic effect in spinal nerve ligation rats. These results demonstrate that chronic pain leads to plasticity of nAChRs that do not directly facilitate nicotine addictive behaviors. Instead, nicotine potently decreases allodynia, an effect that could lead to increased nicotine consumption in chronic pain subjects.
Chronic itch impairs mood and HPA axis function in mice: modulation by CRFR1 antagonist
Authors: Zhao Xin , Yu Chao , Ye Feng , Wang Yan-Gui , Mei Qi-Yong , Ma Qing , Cui Wu-Geng , Zhou Wen-Hua
Published: June 2018

Chronic itch is clinically correlated with the development of mood disorders such as anxiety and depression. Nonetheless, whether this relevance exists in rodents is unknown, and evidence demonstrating chronic itch can affect mood is lacking. The aim of this study is to characterize the affective consequences of chronic itch, and explore potential mechanisms and interventional strategy. We subjected mice to chronic itch by repetitive cutaneous treatment with acetone and diethylether followed by water (AEW) that models “dry skin.” After 3 to 4 weeks AEW treatment, the mice developed behavioral phenotypes of anxiety and depression assessed by a battery of behavioral paradigms, such as light–dark box and forced swim test. These behavioral symptoms of mood disturbance were independent of cutaneous barrier disruption, but correlated well with the degree of the irritating itch sensation. Although AEW mice showed normal circadian hypothalamic-pituitary-adrenal (HPA) axis activity, their neuroendocrine functionality was dampened, including impaired endocrine stress responsivity, altered neuroendocrine–immune interaction, and blunted corticosterone response to both dexamethasone and CRF. Parameters of HPA functionality at the level of mRNA transcripts are altered in stress-related brain regions of AEW mice, implying an overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress axis dysfunction. This is the first evidence revealing mood impairment, HPA axis dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with chronic itch, thus providing a preclinical model to investigate the affective consequence of chronic itch and the underlying mechanisms.
Low- and high-threshold primary afferent inputs to spinal lamina III antenna-type neurons
Authors: Fernandes Elisabete C. , Santos Ines C. , Kokai Eva , Luz Liliana L. , Szucs Peter , Safronov Boris V.
Published: June 2018

The dorsal horn of the spinal cord (laminae I-VI) processes diverse modalities of nociceptive and nonnociceptive sensory information. Antenna-type neurons with cell bodies located in lamina III and large dendritic trees extending from the superficial lamina I to deep lamina IV are best shaped for the integration of a wide variety of inputs arising from primary afferent fibers and intrinsic spinal circuitries. Although the somatodendritic morphology, the hallmark of antenna neurons, has been well studied, little is still known about the axon structure and basic physiological properties of these cells. Here, we did whole-cell recordings in a rat (P9-P12) spinal cord preparation with attached dorsal roots to examine the axon course, intrinsic firing properties, and primary afferent inputs of antenna cells. Nine antenna cells were identified from a large sample of biocytin-filled lamina III neurons (n = 46). Axon of antenna cells showed intensive branching in laminae III-IV and, in half of the cases, issued dorsally directed collaterals reaching lamina I. Antenna cells exhibited tonic and rhythmic firing patterns; single spikes were followed by hyperpolarization or depolarization. The neurons received monosynaptic inputs from the low-threshold Aβ afferents, Aδ afferents, as well as from the high-threshold Aδ, and C afferents. When selectively activated, C-fiber-driven monosynaptic and polysynaptic excitatory postsynaptic potentials were sufficiently strong to evoke firing in the neurons. Thus, lamina III antenna neurons integrate low-threshold and nociceptive high-threshold primary afferent inputs and can function as wide dynamic range neurons able to directly connect deep dorsal horn with the major nociceptive projection area lamina I.
Efficacy of adding interoceptive exposure to intensive interdisciplinary treatment for adolescents with chronic pain: a randomized controlled trial
Authors: Flack Florentina , Stahlschmidt Lorin , Dobe Michael , Hirschfeld Gerrit , Strasser Alexa , Michalak Johannes , Wager Julia , Zernikow Boris
Published: June 2018

Fear of pain plays an important role in the maintenance of chronic pain. It may be reduced through exposure therapy. This 2-arm parallel samples randomized controlled trial aimed to investigate whether interoceptive exposure (IE) therapy enhances reductions in fear of pain (primary outcome), pain (pain intensity, pain-related disability, and school absence), and emotional characteristics (anxiety and catastrophizing) when implemented as an adjunctive treatment in the context of intensive interdisciplinary pain treatment for pediatric chronic pain patients. N = 126 adolescents, aged 11 to 17 years, who were receiving standard intensive interdisciplinary pain treatment were randomly assigned to either receive additional IE (n = 64) or additional relaxation therapy (RT) (n = 62). All patients were assessed at admission, discharge, and 3 months after discharge. The data of N = 104 patients were analyzed. Significant large reductions were found in the total score and subscale scores of the Fear of Pain Questionnaire for Children in both study groups (eg, total score [range 0-60; IE/RT]: admission M = 23.5/24.9; discharge M = 16.0/19.7; P < 0.001,

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= 0.27) and mainly large reductions in pain characteristics. There were no greater decreases in the IE group (P > 0.1). The exploratory analyses revealed that the patients with high fear of pain before treatment (P < 0.05,

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> 0.03) and the patients with abdominal pain (P < 0.04,

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> 0.25) showed greater decreases in their fear of pain (total and subscale score) in the IE group than in the RT group. In conclusion, the results suggest that IE is not particularly effective for all the pediatric chronic pain patients, but the patients with high fear of pain before treatment and with abdominal pain strongly benefit from this intervention.
Vestibular Sclerosis: Is This a New, Distinct Clinicopathological Entity?
Authors: Croker Bethany A. , Scurry James P. , Petry Frances M. , Fischer Gayle
Published: June 2018

Objectives

The aims of this case series were to present a series of patients with clinical and histopathological findings consistent with a recently described condition vestibular sclerosis (VS) and to contribute to the current discussion of whether VS is a subset of lichen sclerosus (LS) or a distinct entity.

Materials and Methods

This case series of 6 women for a 12-month period was initiated from an ongoing collaboration between a gynecological dermatologist and an anatomical pathologist specializing in gynecological dermatopathology.

Results

We describe 6 women with white, hyperkeratotic patches and plaques confined to the vulvar vestibule with stromal sclerosis and an absence of inflammation on histology. All our patients were either perimenopausal or postmenopausal. The condition was either asymptomatic or characterized by mild to moderate dyspareunia. No patient had LS elsewhere on the vulva. There was no response to estrogen or topical corticosteroid therapy in symptomatic patients.

Conclusions

Vestibular sclerosis may be a new distinct clinicopathologial entity, which is in the differential diagnosis of white plaques and patches in the vulvar vestibule. The characteristic siting in the anterior vestibule only, in the presence of an otherwise normal vulva and absence of inflammation on histology, is a reason to separate this condition from LS.
Systematic Review of Treatment Outcome Measures for Vulvodynia
Authors: Sadownik Leslie A. , Yong Paul J. , Smith Kelly B.
Published: June 2018

Objectives of the Study

To systematically evaluate the literature regarding vulvodynia treatment outcome measures.

Methods

A systematic literature search on OVID, PubMed, and PsycINFO databases was conducted from inception until May 2016. Studies were included/excluded based on prespecified criteria. Reported outcome measures were organized into 6 core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT): pain; physical functioning, emotional functioning, participant ratings of global improvement and satisfaction with treatment, symptoms and adverse events, and participant disposition.

Results

Of the 206 articles identified for full-text screening, 33 met our criteria. One study adhered to all IMMPACT recommendations. The number of outcomes measured per study ranged from 1 to greater than 20. Patient-reported pain outcomes were found in the majority (27/33; 82%) of studies. Pain severity with intercourse was reported by 24 (73%) of 33 studies—9 different scales were used to measure this outcome. Clinician-reported outcomes were present in 14 (42%) of 33 studies. Methods of measuring vestibular sensitivity by “cotton swab” test were different in 8 of 10 studies. Other domains reported included; physical function (8/33 studies; 24%), sexual function (23/33 studies; 70%), and emotional function (13/33 studies; 39%). Symptoms and adverse events were reported by 15 (45%) of 33 studies. One study formally reported participant disposition using all the information recommended by CONSORT.

Conclusions

Comparison of clinical trial results in vulvodynia is not possible because of a lack of standard treatment outcome measures. Vulvodynia researchers should apply the IMMPACT criteria to guide the development of a minimum core set of standard outcome measures that measure holistic health.
Cerulein-Induced Acute Pancreatitis Affects Sphingomyelin Signaling Pathway in Rats
Authors: Konończuk Tomasz , Łukaszuk Bartłomiej , Mikłosz Agnieszka , Chabowski Adrian , Żendzian-Piotrowska Małgorzata , Kurek Krzysztof
Published: June 2018

Objectives

Acute pancreatitis (AP) is a common and severe gastrointestinal inflammatory disease with poorly understood pathogenesis. We adopted cerulein-induced pancreatitis, a well-established rat model shearing similarities with human AP, to determine the disease background. Special interest was placed on sphingolipids, because their signaling pathways are involved in many pathological states including hepatic steatosis, heart infarction, or pancreatic origin type 1 diabetes.

Methods

Sphingolipid levels in the blood and pancreas were determined by the means of chromatography (thin-layer and high-performance liquid chromatography).

Results

We found that AP leads to activation of ceramide de novo synthesis pathway, as evidenced by a significant increment in sphinganine, that is, ceramide synthesis precursor, content (+3.8-fold). Surprisingly, despite the reported growth in sphinganine concentration, we observed a reduced (−38%) ceramide level in the pancreas of rats with AP. The results could be explained by subsequent hydrolysis of ceramide to other secondary messengers, that is, sphingosine (+4-fold) or sphingosine-1-phosphate (+3-fold).

Conclusions

Because it is known that sphingosine-1-phosphate and some of its analogs could have a protective role against AP complications, our findings may contribute to elaboration of new therapeutic strategies in the management of this severe medical condition.
Plasma Neurokinin A Levels Predict Survival in Well-Differentiated Neuroendocrine Tumors of the Small Bowel
Authors: Woltering Eugene A. , Voros Brianne A. , Thiagarajan Ramcharan , Beyer David T. , Ramirez Robert A. , Wang Yi-Zarn , Mamikunian Gregg , Boudreaux J. Philip
Published: June 2018

Objectives

Elevated neurokinin A (NKA) levels are associated with poor prognosis in patients with small bowel neuroendocrine tumors. We hypothesized that patients with NKA levels that remain elevated despite treatment with surgical cytoreduction have a poor prognosis.

Methods

Patients diagnosed with small bowel neuroendocrine tumors who underwent surgical cytoreduction at our institution were identified. Demographics, histopathologic characteristics, and biochemical data were collected. Patients were grouped by the trend of their NKA levels (group 1, continuously normal; group 2, transiently elevated but normalized after therapy; group 3, remained elevated despite therapy). Survival rates were calculated from the date of the patient's first NKA level.

Results

Serial NKA values after surgical cytoreduction were monitored in 267 patients. Kaplan-Meier 2-year, 5-year, and 10-year survival rates were as follows: group 1 (n = 157), 97%, 89%, and 62%; group 2 (n = 78), 99%, 90%, and 78%; and group 3 (n = 32), 88%, 69%, and 0%. Survival rates were statistically significant between groups 1 and 3 and between groups 2 and 3 (P < 0.01).

Conclusions

Serial monitoring of plasma NKA levels is useful in identifying patients who have a poor prognosis. Elevated NKA levels can indicate the need for immediate therapeutic intervention.