bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology
Authors: Gazzard Gus , Konstantakopoulou Evgenia , Garway-Heath David , Barton Keith , Wormald Richard , Morris Stephen , Hunter Rachael , Rubin Gary , Buszewicz Marta , Ambler Gareth , Bunce Catey
Published: September 2017

Purpose

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

Design

The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis.

Conclusions

The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication.

Trial registration number

ISRCTN32038223, Pre-results.
Intramuscular tendon involvement on MRI has limited value for predicting time to return to play following acute hamstring injury
Authors: van der Made Anne D , Almusa Emad , Whiteley Rod , Hamilton Bruce , Eirale Cristiano , van Hellemondt Frank , Tol Johannes L
Published: September 2017

Background

Hamstring injury with intramuscular tendon involvement is regarded as a serious injury with a delay in return to play (RTP) of more than 50 days and reinjury rates up to 63%. However, this reputation is based on retrospective case series with high risk of bias.

Objective

Determine whether intramuscular tendon involvement is associated with delayed RTP and elevated rates of reinjury.

Methods

MRI of male athletes with an acute hamstring injury was obtained within 5 days of injury. Evaluation included standardised MRI scoring and scoring of intramuscular tendon involvement. Time to RTP and reinjury rate were prospectively recorded.

Results

Out of 70 included participants, intramuscular tendon disruption was present in 29 (41.4%) injuries. Injuries without intramuscular tendon disruption had a mean time to RTP of 22.2±7.4 days. Injuries with <50%, 50%–99% and 100% disruption of tendon cross-sectional area had a mean time to RTP of 24.0±9.7, 25.3±8.6 and 31.6±10.9 days, respectively. Injuries with full-thickness disruption took longer to RTP compared with injuries without disruption (p=0.025). Longitudinal intramuscular tendon disruption was not significantly associated with time to RTP. Waviness was present in 17 (24.3%) injuries. Mean time to RTP for injuries without and with waviness was 22.6±7.5 and 30.2±10.8 days (p=0.014). There were 11 (15.7%) reinjuries within 12 months, five (17.2%) in the group with intramuscular tendon disruption and six (14.6%) in the group without intramuscular tendon disruption.

Conclusion

Time to RTP for injuries with full-thickness disruption of the intramuscular tendon and waviness is significantly longer (by slightly more than 1 week) compared with injuries without intramuscular tendon involvement. However, due to the considerable overlap in time to RTP between groups with and without intramuscular tendon involvement, its clinical significance for the individual athlete is limited.
Validity of Fitbit’s active minutes as compared with a research-grade accelerometer and self-reported measures
Authors: Brewer Wayne , Swanson Brian T , Ortiz Alexis
Published: September 2017

Objectives

The main purpose of the study was to assess the validity between the Fitbit and ActiGraph GT3X+ accelerometer. The specific aims were to determine the: (1) concurrent validity between the various models of the Fitbit and the GTX3+ accelerometer as the criterion measure for: number of steps and active minutes averaged over a single-day and 7-day period; (2) validity of the two devices with the International Physical Activity Questionnaire (IPAQ) for the number of daily active minutes performed.

Methods

Fifty-three subjects wore a Fitbit and ActiGraph concurrently for 7 days. Data were analysed using correlation coefficients, t-tests to assess mean comparisons and Bland-Altman plots to determine agreement between the Fitbit and the ActiGraph.

Results

The correlations between the Fitbit and ActiGraph for steps per day and per 7 days were r=0.862 and 0.820, respectively with significant mean differences between both devices. Bland-Altman analyses revealed agreement between the Fitbit and the ActiGraph for 7-day active minutes only. The correlations between the Fitbit and ActiGraph for active minutes per day and per 7 days were r=0.695 and r=0.658, respectively, with no significant mean differences between both devices. No significant correlations were found between the IPAQ and the other two devices.

Conclusions

The data produced by the Fitbit were consistent with the ActiGraph when the means of each device were compared over the 1-day and 7-day time periods. However, Bland-Altman analyses revealed that the Fitbit agreed with the ActiGraph when used to measure physical activity levels over a 7-day span only.
Vitamin D supplementation to palliative cancer patients: protocol of a double-blind, randomised controlled trial ‘Palliative-D’
Authors: Helde-Frankling Maria , Bergqvist Jenny , Klasson Caritha , Nordström Marie , Höijer Jonas , Bergman Peter , Björkhem-Bergman Linda
Published: September 2017

Background

According to a small pilot study on palliative cancer patients at our ward, vitamin D supplementation had beneficial effects on pain (measured as opioid consumption), infections and quality of life (QoL) without having any significant side effects.

Objective

The primary objective of the ‘Palliative-D’ study is to test the hypothesis that vitamin D supplementation for 12 weeks reduces opioid consumption. The secondary objectives are to study if reduction of antibiotic consumption and fatigue as well as improvement in QoL assessments can be observed. Effect on the 25-hydroxy vitamin D (25-OHD) levels in serum after 12 weeks of treatment will be studied, as well as the change in opioid dose in relation to genetic polymorphism in genes involved in the effect and metabolism of vitamin D.

Method

A randomised, double-blind placebo-controlled multicentre trial has been designed. The trial will include 254 adult palliative cancer patients with 25-OHD levels <50 nmol/L and a life expectancy of more than 3 months recruited from two advanced palliative home care centres in Stockholm. Included patients will be randomly assigned to 12 weeks of treatment with cholecalciferol (vitamin D3) 4000 IU/day or placebo. The study will start in November 2017 and will finish in December 2019. The study is approved by the Regional Ethical Committee, Dnr2017/405-31/1, by the Swedish Medical Products Agency, EudraCT: 2017-000268-14, and is registered at Clinicaltrial.gov:NCT03038516. The study is financed with research grants from the Swedish Cancer Society and the Stockholm County Council.
Application of sequential proline-catalyzed α-chlorination and aldol reactions in the total synthesis of 1-deoxygalactonojirimycin
Authors: Meanwell Michael , Sutherland Mathew , Britton Robert
Published: September 2017

A short enantioselective total synthesis of 1-deoxygalactonojirimycin (migalastat) has been achieved that does not rely on chiral pool starting materials or biocatalysis. Instead, this synthesis exploits a one-pot proline-catalyzed α-chlorination and aldol reaction of a commercially available aldehyde to assemble the entire carbon skeleton in a single step. The key role played by a nitrogen protecting group in the final epoxide opening reaction is highlighted as is the amenability to access structural analogues using this route.
Adaptive Point Location in Planar Convex Subdivisions
Authors: Cheng Siu-Wing , Lau Man-Kit
Published: September 2017

We present a planar point location structure for a convex subdivision [Formula: see text]. Given a query sequence of length [Formula: see text], the total running time is [Formula: see text], where [Formula: see text] is the number of vertices in [Formula: see text] and [Formula: see text] is the minimum time required by any linear decision tree for answering planar point location queries in [Formula: see text] to process the same query sequence. The running time includes the preprocessing time. Therefore, for [Formula: see text], our running time is only worse than the best possible bound by [Formula: see text] per query, which is much smaller than the [Formula: see text] query time offered by a worst-case optimal planar point location structure.
Buckling Behavior of Non-Uniformly Heated Tapered Laminated Composite Plates with Ply Drop-Off
Authors: Ashok Shushanth , Pitchaimani Jeyaraj
Published: September 2017

The thermal buckling characteristics of non-uniformly heated tapered laminated composites plates with ply drop-off have been investigated numerically. Detailed parametric studies have been carried out for the effects of taper configuration, temperature variation, aspect ratio and structural boundary conditions on critical buckling temperatures and buckling mode shapes. It is found that the nature of taper as well as the applied temperature field have considerable effects on the critical buckling temperatures of laminated composite tapered plates. Square plates buckle at the highest temperature when subjected to the decreasing temperature profile. Additionally, it is noted that Taper B and Taper C plates show the best behavior under buckling for most structural boundary conditions. Moreover, the change in buckling mode shapes with respect to temperature profile and taper configuration is significant for rectangular plates in comparison with square plates.
(Pro)renin receptor mediates albumin-induced cellular responses: role of site-1 protease-derived soluble (pro)renin receptor in renal epithelial cells
Authors: Fang Hui , Xu Chuanming , Lu Aihua , Zou Chang-Jiang , Xie Shiying , Chen Yanting , Zhou Li , Liu Mi , Wang Lei , Wang Weidong , Yang Tianxin
Published: September 2017

Proteinuria is a characteristic of chronic kidney disease and also a causative factor that promotes the disease progression, in part, via activation of the intrarenal renin-angiotensin system (RAS). (Pro)renin receptor (PRR), a newly discovered component of the RAS, binds renin and (pro)renin to promote angiotensin I generation. The present study was performed to test the role of soluble PRR (sPRR) in albumin overload-induced responses in cultured human renal proximal tubular cell line human kidney 2 (HK-2) cells. Bovine serum albmuin (BSA) treatment for 24 h at 20 mg/ml induced renin activity and inflammation, both of which were attenuated by a PRR decoy inhibitor PRO20. BSA treatment induced a more than fivefold increase in medium sPRR due to enhanced cleavage of PRR. Surprisingly, this cleavage event was unaffected by inhibition of furin or a disintegrin and metalloproteinase 19. Screening for a novel cleavage enzyme led to the identification of site-1 protease (S1P). Inhibition of S1P with PF-429242 or siRNA remarkably suppressed BSA-induced sPRR production, renin activity, and inflammatory response. Administration of a recombinant sPRR, termed sPRR-His, reversed the effects of S1P inhibition. In HK-2 cells overexpressing PRR, mutagenesis of the S1P, but not furin cleavage site, reduced sPRR levels. Together, these results suggest that PRR mediates albumin-induced cellular responses through S1P-derived sPRR.
Obesity modulates diaphragm curvature in subjects with and without COPD
Authors: Boriek Aladin M. , Lopez Michael A. , Velasco Cristina , Bakir Azam A. , Frolov Anna , Wynd Shari , Babb Tony G. , Hanania Nicola A. , Hoffman Eric A. , Sharafkhaneh Amir
Published: September 2017

Obesity is a common comorbidity of chronic obstructive pulmonary disease (COPD) and has been associated with worse outcomes. However, it is unknown whether the interaction between obesity and COPD modulates diaphragm shape and consequently its function. The body mass index (BMI) has been used as a correlate of obesity. We tested the hypothesis that the shape of the diaphragm muscle and size of the ring of its insertion in non-COPD and COPD subjects are modulated by BMI. We recruited 48 COPD patients with postbronchiodilator forced expiratory volume in 1 s (FEV1)-to-forced vital capacity (FVC) < 0.7 and 29 age-matched smoker/exsmoker control (non-COPD) subjects, who underwent chest computed tomography (CT) at lung volumes ranging from functional residual capacity (FRC) to total lung capacity (TLC). We then computed maximum principal diaphragm curvature in the midcostal region of the left hemidiaphragm at the end of inspiration during quiet breathing (EI) and at TLC. The radius of maximum curvature of diaphragm muscle increased with BMI in both COPD and non-COPD subjects. The size of diaphragm ring of insertion on the chest wall also increased significantly with increasing BMI. Surprisingly, COPD severity did not appear to cause significant alteration in diaphragm shape except in normal-weight subjects at TLC. Our data uncovered important factors such as BMI, the size of the diaphragm ring of insertion, and disease severity that modulate the structure of the ventilatory pump in non-COPD and COPD subjects.
Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells
Authors: Khani Mohammad Hossein , Gollisch Tim
Published: September 2017

Retinal ganglion cells adapt to changes in visual contrast by adjusting their response kinetics and sensitivity. While much work has focused on the time scales of these adaptation processes, less is known about the spatial scale of contrast adaptation. For example, do small, localized contrast changes affect a cell’s signal processing across its entire receptive field? Previous investigations have provided conflicting evidence, suggesting that contrast adaptation occurs either locally within subregions of a ganglion cell’s receptive field or globally over the receptive field in its entirety. Here, we investigated the spatial extent of contrast adaptation in ganglion cells of the isolated mouse retina through multielectrode-array recordings. We applied visual stimuli so that ganglion cell receptive fields contained regions where the average contrast level changed periodically as well as regions with constant average contrast level. This allowed us to analyze temporal stimulus integration and sensitivity separately for stimulus regions with and without contrast changes. We found that the spatial scope of contrast adaptation depends strongly on cell identity, with some ganglion cells displaying clear local adaptation, whereas others, in particular large transient ganglion cells, adapted globally to contrast changes. Thus, the spatial scope of contrast adaptation in mouse retinal ganglion cells appears to be cell-type specific. This could reflect differences in mechanisms of contrast adaptation and may contribute to the functional diversity of different ganglion cell types.

NEW & NOTEWORTHY Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity in spatial scope can contribute to the functional diversity of retinal ganglion cell types.
Comparison of three models of saccade disconjugacy in strabismus
Authors: Walton Mark M. G. , Mustari Michael J.
Published: September 2017

In pattern strabismus the horizontal and vertical misalignments vary with eye position along the orthogonal axis. The disorder is typically described in terms of overaction or underaction of oblique muscles. Recent behavioral studies in humans and monkeys, however, have reported that such actions are insufficient to fully explain the patterns of directional and amplitude disconjugacy of saccades. There is mounting evidence that the oculomotor abnormalities associated with strabismus are at least partially attributable to neurophysiological abnormalities. A number of control systems models have been developed to simulate the kinematic characteristics of saccades in normal primates. In the present study we sought to determine whether these models could simulate the abnormalities of saccades in strabismus by making two assumptions: 1) in strabismus the burst generator gains differ for the two eyes and 2) abnormal crosstalk exists between the horizontal and vertical saccadic circuits in the brain stem. We tested three models, distinguished by the location of the horizontal-vertical crosstalk. All three models were able to simulate amplitude and directional saccade disconjugacy, postsaccadic drift, and a pattern strabismus for static fixation, but they made different predictions about the dynamics of saccades. By assuming that crosstalk occurs at multiple nodes, the Distributed Crosstalk Model correctly predicted the dynamics of saccades. These new models make additional predictions that can be tested with future neurophysiological experiments.

NEW & NOTEWORTHY Over the past several decades, numerous control systems models have been devised to simulate the known kinematic features of saccades in normal primates. These models have proven valuable to neurophysiology, as a means of generating testable predictions. The present manuscript, as far as we are aware, is the first to present control systems models to simulate the known abnormalities of saccades in strabismus.
Spatial-Temporal Similarity Correlation between Public Transit Passengers Using Smart Card Data
Authors: Faroqi Hamed , Mesbah Mahmoud , Kim Jiwon
Published: September 2017

The increasing availability of public transit smart card data has enabled several studies to focus on identifying passengers with similar spatial and/or temporal trip characteristics. However, this paper goes one step further by investigating the relationship between passengers’ spatial and temporal characteristics. For the first time, this paper investigates the correlation of the spatial similarity with the temporal similarity between public transit passengers by developing spatial similarity and temporal similarity measures for the public transit network with a novel passenger-based perspective. The perspective considers the passengers as agents who can make multiple trips in the network. The spatial similarity measure takes into account direction as well as the distance between the trips of the passengers. The temporal similarity measure considers both the boarding and alighting time in a continuous linear space. The spatial-temporal similarity correlation between passengers is analysed using histograms, Pearson correlation coefficients, and hexagonal binning. Also, relations between the spatial and temporal similarity values with the trip time and length are examined. The proposed methodology is implemented for four-day smart card data including 80,000 passengers in Brisbane, Australia. The results show a nonlinear spatial-temporal similarity correlation among the passengers.
The Impact of Adherence and Instillation Proficiency of Topical Glaucoma Medications on Intraocular Pressure
Authors: Atey Tesfay Mehari , Shibeshi Workineh , T. Giorgis Abeba , Asgedom Solomon Weldegebreal
Published: September 2017

Background. The possible sequel of poorly controlled intraocular pressure (IOP) includes treatment failure, unnecessary medication use, and economic burden on patients with glaucoma. Objective. To assess the impact of adherence and instillation technique on IOP control. Methods. A cross-sectional study was conducted on 359 glaucoma patients in Menelik II Hospital from June 1 to July 31, 2015. After conducting a Q-Q analysis, multiple binary logistic analyses, linear regression analyses, and two-tailed paired t-test were conducted to compare IOP in the baseline versus current measurements. Results. Intraocular pressure was controlled in 59.6% of the patients and was relatively well controlled during the study period (mean (M) = 17.911 mmHg, standard deviation (S) = 0.323) compared to the baseline (M=20.866 mmHg, S=0.383, t (358) = −6.70, p<0.0001). A unit increase in the administration technique score resulted in a 0.272 mmHg decrease in IOP (p=0.03). Moreover, primary angle-closure glaucoma (adjusted odds ratio (AOR) = 0.347, 95% confidence interval (CI): 0.144–0.836) and two medications (AOR = 1.869, 95% CI: 1.259–9.379) were factors affecting IOP. Conclusion. Good instillation technique of the medications was correlated with a reduction in IOP. Consequently, regular assessment of the instillation technique and IOP should be done for better management of the disease.
Effect of Multicomponent Training on Blood Pressure, Nitric Oxide, Redox Status, and Physical Fitness in Older Adult Women: Influence of Endothelial Nitric Oxide Synthase (NOS3) Haplotypes
Authors: Trapé Atila Alexandre , Lizzi Elisangela Aparecida da Silva , Gonçalves Thiago Correa Porto , Rodrigues Jhennyfer Aline Lima , Tavares Simone Sakagute , Lacchini Riccardo , Pinheiro Lucas Cezar , Ferreira Graziele Cristina , Tanus-Santos José Eduardo , Ovídio Paula Payão , Jordão Alceu Afonso , Jacomini André Mourão , Zago Anderson Saranz , Bueno Júnior Carlos Roberto
Published: September 2017

The purpose of this study was to verify the influence of the genotype or haplotype (interaction) of the NOS3 polymorphisms [‐786T>C, 894G>T (Glu298Asp), and intron 4b/a] on the response to multicomponent training (various capacities and motor skills) on blood pressure (BP), nitrite concentration, redox status, and physical fitness in older adult women. The sample consisted of 52 participants, who underwent body mass index and BP assessments. Physical fitness was evaluated by six‐minute walk, elbow flexion, and sit and stand up tests. Plasma/blood samples were used to evaluate redox status, nitrite concentration, and genotyping. Associations were observed between isolated polymorphisms and the response of decreased systolic and diastolic BP and increased nitrite concentration and antioxidant activity. In the haplotype analysis, the group composed of ancestral alleles (H1) was the only one to present improvement in all variables studied (decrease in systolic and diastolic BP, improvement in nitrite concentration, redox status, and physical fitness), while the group composed of variant alleles (H8) only demonstrated improvement in some variables of redox status and physical fitness. These findings suggest that NOS3 polymorphisms and physical training are important interacting variables to consider in evaluating redox status, nitric oxide availability and production, and BP control.
Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus
Authors: Eyileten Ceren , Kaplon-Cieslicka Agnieszka , Mirowska-Guzel Dagmara , Malek Lukasz , Postula Marek
Published: September 2017

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM). BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM.
Cloud Base Height Estimation from ISCCP Cloud-Type Classification Applied to A-Train Data
Authors: Liang Yao , Sun Xuejin , Miller Steven D. , Li Haoran , Zhou Yongbo , Zhang Riwei , Li Shaohui
Published: September 2017

Cloud base height (CBH) is an important cloud macro parameter that plays a key role in global radiation balance and aviation flight. Building on a previous algorithm, CBH is estimated by combining measurements from CloudSat/CALIPSO and MODIS based on the International Satellite Cloud Climatology Project (ISCCP) cloud-type classification and a weighted distance algorithm. Additional constraints on cloud water path (CWP) and cloud top height (CTH) are introduced. The combined algorithm takes advantage of active and passive remote sensing to effectively estimate CBH in a wide-swath imagery where the cloud vertical structure details are known only along the curtain slice of the nonscanning active sensors. Comparisons between the estimated and observed CBHs show high correlation. The coefficient of association (R2) is 0.8602 with separation distance between donor and recipient points in the range of 0 to 100 km and falls off to 0.5856 when the separation distance increases to the range of 401 to 600 km. Also, differences are mainly within 1 km when separation distance ranges from 0 km to 600 km. The CBH estimation method was applied to the 3D cloud structure of Tropical CycloneBill, and the method is further assessed by comparing CTH estimated by the algorithm with the MODIS CTH product.
Fundamental Results of Conformable Sturm-Liouville Eigenvalue Problems
Authors: Al-Refai Mohammed , Abdeljawad Thabet
Published: September 2017

We suggest a regular fractional generalization of the well-known Sturm-Liouville eigenvalue problems. The suggested model consists of a fractional generalization of the Sturm-Liouville operator using conformable derivative and with natural boundary conditions on bounded domains. We establish fundamental results of the suggested model. We prove that the eigenvalues are real and simple and the eigenfunctions corresponding to distinct eigenvalues are orthogonal and we establish a fractional Rayleigh Quotient result that can be used to estimate the first eigenvalue. Despite the fact that the properties of the fractional Sturm-Liouville problem with conformable derivative are very similar to the ones with the classical derivative, we find that the fractional problem does not display an infinite number of eigenfunctions for arbitrary boundary conditions. This interesting result will lead to studying the problem of completeness of eigenfunctions for fractional systems.
Successful Treatment of Hemophagocytic Lymphohistiocytosis Associated with Lupus Nephritis by Using Mycophenolate Mofetil
Authors: Nawata Takashi , Kubo Makoto , Shiragami Kosaku , Nakamura Yukinori , Yano Masafumi
Published: September 2017

An estimated 0.9% to 2.4% of patients with systemic lupus erythematosus (SLE) also have hemophagocytic lymphohistiocytosis (HLH). HLH associated with autoimmune diseases is often refractory to corticosteroid treatment; thus, additional immunosuppressive drugs, such as cyclosporine, cyclophosphamide, or tacrolimus, are required. Here, we describe the case of a 44-year-old Japanese woman who developed HLH associated with lupus nephritis. Initially, her HLH was refractory to treatment with a corticosteroid, tacrolimus, and mizoribine. However, alternative treatment with a corticosteroid, mycophenolate mofetil, and tacrolimus improved both her HLH and lupus nephritis. This case suggests the possibility of mycophenolate mofetil as a key drug for treating HLH associated with SLE.
Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice
Authors: Lu Yifan , Jiang Lu , Li Wanlu , Qu Meijie , Song Yaying , He Xiaosong , Zhang Zhijun , Yang Guo-Yuan , Wang Yongting
Published: September 2017

Neural stem cell (NSC) transplantation is a promising treatment to improve the recovery after brain ischemia. However, how the survival, proliferation, migration, and differentiation of implanted NSC are influenced by endogenous neuronal activity remains unclear. In this work, we used optogenetic techniques to control the activity of striatal neurons and investigated how their activity affected the survival and migration of transplanted NSCs and overall neurological outcome after ischemic stroke. NSCs cultured from transgenic mice expressing fluorescent protein were transplanted into the peri-infarct region of the striatum after transient middle cerebral artery occlusion (tMCAO) surgery. The striatal neurons were excited or inhibited for 15 minutes daily via implanted optical fiber after tMCAO. The results revealed that mice which received NSC transplantation and optogenetic inhibition had smaller brain infarct volume and increased NSC migration compared to the NSC alone or PBS group (p<0.05). In contrast, mice which received NSC transplantation and optogenetic excitation showed no difference in infarct volume and neurological behavior improvement compared to the PBS control group. In vitro experiments further revealed that the conditioned media from excited GABAergic neurons reduced NSC viability through paracrine mechanisms.Conclusion. Optogenetic inhibition of striatal neuronal activity further improved neurological recovery after NSC transplantation at the subacute phase after brain ischemia.
Metastatic Sarcomatoid Squamous Cell Carcinoma of the Cervix Presenting with Chest Mass
Authors: Karapetyan Lilit , Rai Manoj , Dawani Om , Laird-Fick Heather S.
Published: September 2017

Background. Sarcomatoid squamous cell carcinoma is a rare and aggressive form of cervical cancer. We report a case of metastatic sarcomatoid squamous cell carcinoma (SSCC) of cervix that presented with an anterior chest wall mass. Case. A 43-year-old Hispanic female presented with a two-month history of a central chest wall mass. The patient’s only past medical history was SSCC of the cervix, stage IIB, diagnosed two years priorly. She underwent neoadjuvant chemoradiation therapy (CRT) with cisplatin followed by radical hysterectomy. Surgical margins were positive which led to adjuvant CRT with carboplatin and paclitaxel. PET scan 4 months after the postoperative treatment was negative for recurrence and metastatic disease. On current presentation, the CT chest revealed anterior mediastinal destructive soft tissue mass involving sternum, and the biopsy showed SSCC. The patient received palliative radiation therapy to her chest with improvement in pain and ability to swallow. After discussing the prognosis she refused further chemotherapy and decided on hospice care. Conclusion. Despite good response to first-line therapy, SSCC tends to recur early and does not respond to second-line therapy. Radiation therapy seems to be the most effective modality for treatment, but randomized controlled trials of therapy are impractical.
Trajectories of Postload Plasma Glucose in the Development of Type 2 Diabetes in Japanese Adults
Authors: Oka Rie , Shibata Kyoko , Sakurai Masaru , Kometani Mitsuhiro , Yamagishi Masakazu , Yoshimura Kenichi , Yoneda Takashi
Published: September 2017

We aimed to clarify how the trajectories of 1-hour postload plasma glucose (PG) and 2-hour PG were different in the development of type 2 diabetes. Using data of repeated health checkups in Japanese workers from April 2006 to March 2016, longitudinal changes of fasting, 1-hour, and 2-hour PG on the oral glucose tolerance test were analyzed with a linear mixed effects model. Of the 1464 nondiabetic subjects at baseline, 112 subjects progressed to type 2 diabetes during the observation period (progressors). In progressors, 1-hour PG and 2-hour PG showed gradual increases with slopes of 1.33 ± 0.2 and 0.58 ± 0.2 mg/dL/year, respectively, followed by a steep increase by which they attained diabetes. Until immediately before the diabetes transition, age- and sex-adjusted mean level of 2-hour PG was 149 ± 2.7 mg/dL, 34 ± 2.7 (30%) higher compared to nonprogressors, while that of 1-hour PG was 206 ± 4.1 mg/dL, 60 ± 4.3 mg/dL (41%) higher compared to nonprogressors. In conclusion, diabetes transition was preceded by a mild elevation of 2-hour PG for several years or more. The elevation in 1-hour PG was larger than that of 2-hour PG until immediately before the transition to diabetes.
Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy
Authors: Villalobos-Labra Roberto , Silva Luis , Subiabre Mario , Araos Joaquín , Salsoso Rocío , Fuenzalida Bárbara , Sáez Tamara , Toledo Fernando , González Marcelo , Quezada Claudia , Pardo Fabián , Chiarello Delia I. , Leiva Andrea , Sobrevia Luis
Published: September 2017

Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium.
Systematic Identification and Molecular Characteristics of Long Noncoding RNAs in Pig Tissues
Authors: Yang Yalan , Zhou Rong , Zhu Shiyun , Li Xunbi , Li Hua , Yu Hui , Li Kui
Published: September 2017

Long noncoding RNAs (lncRNAs) are non-protein-coding RNAs that are involved in a variety of biological processes. The pig is an important farm animal and an ideal biomedical model. In this study, we performed a genome-wide scan for lncRNAs in multiple tissue types from pigs. A total of 118 million paired-end 90 nt clean reads were obtained via strand-specific RNA sequencing, 80.4% of which were aligned to the pig reference genome. We developed a stringent bioinformatics pipeline to identify 2,139 high-quality multiexonic lncRNAs. The characteristic analysis revealed that the novel lncRNAs showed relatively shorter transcript length, fewer exons, and lower expression levels in comparison with protein-coding genes (PCGs). The guanine-cytosine (GC) content of the protein-coding exons and introns was significantly higher than that of the lncRNAs. Moreover, the single nucleotide polymorphism (SNP) density of lncRNAs was significantly higher than that of PCGs. Conservation analysis revealed that most lncRNAs were evolutionarily conserved among pigs, humans, and mice, such as CUFF.253988.1, which shares homology with human long noncoding RNA MALAT1. The findings of our study significantly increase the number of known lncRNAs in pigs.
Impact of Spasticity on Balance Control during Quiet Standing in Persons after Stroke
Authors: Rahimzadeh Khiabani Reza , Mochizuki George , Ismail Farooq , Boulias Chris , Phadke Chetan P. , Gage William H.
Published: September 2017

Background. Balance impairments, falls, and spasticity are common after stroke, but the effect of spasticity on balance control after stroke is not well understood.Methods. In this cross-sectional study, twenty-seven participants with stroke were divided into two groups, based on ankle plantar flexor spasticity level. Fifteen individuals with high spasticity (Modified Ashworth Scale (MAS) score of ≥2) and 12 individuals with low spasticity (MAS score <2) completed quiet standing trials with eyes open and closed conditions. Balance control measures included centre of pressure (COP) root mean square (RMS), COP velocity, and COP mean power frequency (MPF) in anterior-posterior and mediolateral (ML) directions. Trunk sway was estimated using a wearable inertial measurement unit to measure trunk angle, trunk velocity, and trunk velocity frequency amplitude in pitch and roll directions.Results. The high spasticity group demonstrated greater ML COP velocity, trunk roll velocity, trunk roll velocity frequency amplitude at 3.7 Hz, and trunk roll velocity frequency amplitude at 4.9 Hz, particularly in the eyes closed condition (spasticitybyvisioninteraction). ML COP MPF was greater in the high spasticity group.Conclusion. Individuals with high spasticity after stroke demonstrated greater impairment of balance control in the frontal plane, which was exacerbated when vision was removed.
Analysis of Adverse Events during Intrahospital Transportation of Critically Ill Patients
Authors: Gimenez Francielli Mary Pereira , Camargo Wesley Henrique Bueno de , Gomes Ana Clara Beraldo , Nihei Thaylla Sumyre , Andrade Monique Walicheki Maria , Valverde Maria Laura de A. F. Sé , Campos Larissa D’ Epiro de Souza , Grion Debora Carvalho , Festti Josiane , Grion Cintia Magalhães Carvalho
Published: September 2017

Purpose. To describe adverse events occurring during intrahospital transportation of adult patients hospitalized in an Intensive Care Unit (ICU) and to evaluate the association with morbidity and mortality.Method. Prospective cohort study from July 2014 to July 2015. Data collection comprised clinical data, prognostic scores, length of stay, and outcome at hospital discharge. Data was collected on transport and adverse events. Adverse events were classified according to the World Health Organization following the degree of damage. The level of significance was set at 5%.Results. A total of 293 patients were analyzed with follow-up of 143 patient transportations and records of 86 adverse events. Of these events, 44.1% were related to physiological alterations, 23.5% due to equipment failure, 19.7% due to team failure, and 12.7% due to delays. Half of the events were classified as moderate. The mean time of hospital stay of the group with adverse events was higher compared to patients without adverse events (31.4 versus 16.6 days, resp.,p<0.001).Conclusions. Physiological alterations were the most frequently encountered events, followed by equipment and team failures. The degree of damage associated with adverse events was classified as moderate and associated with an increase in the length of hospital stay.
Hem-o-lok Clips Migration: An Easily Neglected Complication after Laparoscopic Biliary Surgery
Authors: Qu Jun-wen , Wang Gui-yang , Yuan Zhi-qing , Li Ke-wei
Published: September 2017

Clip migration into the common bile duct (CBD) is a rare but well-established phenomenon of laparoscopic biliary surgery. The mechanism and exact incidence of clip migration are both poorly understood. Clip migration into the common bile duct can cause recurrent cholangitis and serve as a nidus for stone formation. We present a case, a 54-year-old woman, of clip-induced cholangitis resulting from surgical clip migration 12 months after laparoscopic cholecystectomy and laparoscopic common bile duct exploration (LC+LCBDE) with primary closure.
A Signal Decomposition Method for Ultrasonic Guided Wave Generated from Debonding Combining Smoothed Pseudo Wigner-Ville Distribution and Vold–Kalman Filter Order Tracking
Authors: Wu Junhua , Chen Xinglin , Ma Zheshu
Published: September 2017

Carbon fibre composites have a promising application future of the vehicle, due to its excellent physical properties. Debonding is a major defect of the material. Analyses of wave packets are critical for identification of the defect on ultrasonic nondestructive evaluation and testing. In order to isolate different components of ultrasonic guided waves (GWs), a signal decomposition algorithm combining Smoothed Pseudo Wigner-Ville distribution and Vold–Kalman filter order tracking is presented. In the algorithm, the time-frequency distribution of GW is first obtained by using Smoothed Pseudo Wigner-Ville distribution. The frequencies of different modes are computed based on summation of the time-frequency coefficients in the frequency direction. On the basis of these frequencies, isolation of different modes is done by Vold–Kalman filter order tracking. The results of the simulation signal and the experimental signal reveal that the presented algorithm succeeds in decomposing the multicomponent signal into monocomponents. Even though components overlap in corresponding Fourier spectrum, they can be isolated by using the presented algorithm. So the frequency resolution of the presented method is promising. Based on this, we can do research about defect identification, calculation of the defect size, and locating the position of the defect.
Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice
Authors: Sung Yoon-Young , Kim Seung-Hyung , Kim Dong-Seon , Lee Ji-eun , Kim Ho Kyoung
Published: September 2017

Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans-anethole (AET), on airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3) expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness (p<0.01), pulmonary eosinophilic infiltration (p<0.05), mucus hypersecretion (p<0.01), and IL-4, IL-5, IL-13, and CCR3 production (p<0.05), as well as IgE levels (p<0.01). IVE and AET increased Foxp3 expression in lungs (p<0.05). IVE and AET reduced IL-4 and increased IFN-γ production in the supernatant of splenocyte cultures (p<0.05). Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p<0.01). These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3+ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.
Extension of Wolfe Method for Solving Quadratic Programming with Interval Coefficients
Authors: Syaripuddin  , Suprajitno Herry , Fatmawati
Published: September 2017

Quadratic programming with interval coefficients developed to overcome cases in classic quadratic programming where the coefficient value is unknown and must be estimated. This paper discusses the extension of Wolfe method. The extended Wolfe method can be used to solve quadratic programming with interval coefficients. The extension process of Wolfe method involves the transformation of the quadratic programming with interval coefficients model into linear programming with interval coefficients model. The next step is transforming linear programming with interval coefficients model into two classic linear programming models with special characteristics, namely, the optimum best and the worst optimum problem.
Propyl Gallate Exerts an Antimigration Effect on Temozolomide-Treated Malignant Glioma Cells through Inhibition of ROS and the NF-κB Pathway
Authors: Yang Jen-Tsung , Lee I-Neng , Lu Fung-Jou , Chung Chiu-Yen , Lee Ming-Hsueh , Cheng Yu-Ching , Chen Kuo-Tai , Chen Ching-Hsein
Published: September 2017

In this study, we demonstrated that temozolomide (TMZ) and propyl gallate (PG) combination enhanced the inhibition of migration in human U87MG glioma cells. PG inhibited the TMZ-induced reactive oxygen species (ROS) generation. The mitochondrial complex III and NADPH oxidase are two critical sites that can be considered to regulate antimigration in TMZ-treated U87MG cells. PG can enhance the antimigration effect of TMZ through suppression of metalloproteinase-2 and metalloproteinase-9 activities, ROS generation, and the NF-κB pathway and possibly provide a novel prospective strategy for treating malignant glioma.
CCR5-Dependent Homing of T Regulatory Cells to the Tumor Microenvironment Contributes to Skin Squamous Cell Carcinoma Development
Authors: de Oliveira Carine Ervolino , Gasparoto Thaís Helena , Pinheiro Claudia Ramos , Amôr Nádia Ghinelli , Nogueira Maria Renata Sales , Kaneno Ramon , Garlet Gustavo Pompermaier , Lara Vanessa Soares , Silva João Santana , Cavassani Karen Angélica , Campanelli Ana Paula
Published: September 2017

Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5- and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice. Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. Moreover, the adoptive transfer of naturally occurring Tregs CD4+CD25+CCR5+, CD4+CD25−CCR5+ or CD8+CCR5+ conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. Interestingly, adoptive transfer of WT CD4+CD25+CCR5+ cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8+ T cells. Our findings reinforce the therapeutic potential of CCR5 inhibition for cancer treatment, and indicate an attractive approach for SCC treatment. Mol Cancer Ther; 16(12); 2871–80. ©2017 AACR.