bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma
Authors: Konjević Gordana , Vuletić Ana , Mirjačić Martinović Katarina , Colović Nataša , Čolović Milica , Jurišić Vladimir
Published: April 2016

Aim

As innate immune cells natural killer (NK), NK-like T and CTLγδ are important in antitumour response in multiple myeloma (MM), the aim of this study was to investigate some functional and phenotypical characteristics of these cells in MM.

Methods

29 patients with MM prior to therapy, in clinical stage I-III and 15 healthy controls (HCs) were investigated. Percent of immune cells in peripheral blood, NK cell activity, expression of activating (CD161) and inhibitory (CD158a, CD158b) NK cell receptors on CD3−CD16+NK cells were evaluated using 51-chromium-release assay and by flow cytometry. Production of interleukin (IL) 2 and tumour necrosis factor (TNF)α was analysed in supernatants from in vitro activated peripheral blood mononuclear cells.

Results

In patients with MM the percent of NK cells and their two subsets did not differ from controls, while NK-like T and CTLγδ cells were significantly decreased. Significant impairment of NK cell cytotoxicity, CD107a expression and interferon γ intracellular level was also shown. There was a significant decrease in CD161 and an increase in CD158a receptor expression on NK cells in these patients. Also IL-2 production was lowest in clinical stage III. However, TNF-α production did not differ between patients and HCs.

Conclusions

Altered expression of CD161 activating and CD158a KIR inhibitory receptor is responsible for impaired antitumour activity of NK cells in MM patients. These new biomarkers may be helpful for patient selection for immunotherapy with cytokines, and novel KIR blocking monoclonal antibodies that enhance NK cell antimyeloma activity and provide clinical benefit.
2016 Laboratory guidelines for postvasectomy semen analysis: Association of Biomedical Andrologists, the British Andrology Society and the British Association of Urological Surgeons
Authors: Hancock P , Woodward B J , Muneer A , Kirkman-Brown J C
Published: April 2016

Post-vasectomy semen analysis (PVSA) is the procedure used to establish whether sperm are present in the semen following a vasectomy. PVSA is presently carried out by a wide variety of individuals, ranging from doctors and nurses in general practitioner (GP) surgeries to specialist scientists in andrology laboratories, with highly variable results.

Key recommendations are that: (1) PVSA should take place a minimum of 12 weeks after surgery and after a minimum of 20 ejaculations. (2) Laboratories should routinely examine samples within 4 h of production if assessing for the presence of sperm. If non-motile sperm are observed, further samples must be examined within 1 h of production. (3) Assessment of a single sample is acceptable to confirm vasectomy success if all recommendations and laboratory methodology are met and no sperm are observed. Clearance can then be given. (4) The level for special clearance should be <100 000/mL non-motile sperm. Special clearance cannot be provided if any motile sperm are observed and should only be given after assessment of two samples in full accordance with the methods contained within these guidelines. Surgeons are responsible both preoperatively and postoperatively for the counselling of patients and their partners regarding complications and the possibility of late recanalisation after clearance. These 2016 guidelines replace the 2002 British Andrology Society (BAS) laboratory guidelines and should be regarded as definitive for the UK in the provision of a quality PVSA service, accredited to ISO 15189:2012, as overseen by the United Kingdom Accreditation Service (UKAS).
Acute management and outcomes of iatrogenic dissections during cerebral angiography
Authors: Groves Andrew P , Kansagra Akash P , Cross DeWitte T , Moran Christopher J , Derdeyn Colin P
Published: April 2016

Background and purpose

Iatrogenic dissection is a known complication of cerebral angiography, but the clinical outcomes and optimal treatment of these patients is not well established. We sought to review our experience with cerebral angiography to determine the incidence of iatrogenic dissections along with clinical outcomes associated with a generally conservative treatment strategy.

Materials and methods

We retrospectively reviewed clinical records for all patients that underwent cerebral angiography between March 2002 and May 2015. Demographic information, angiography reports, follow-up CT and MRI reports, and follow-up clinical notes were reviewed.

Results

17 418 cerebral angiograms were performed during the review period, including 13 485 diagnostic angiograms and 3933 endovascular interventional procedures. 68 iatrogenic dissections were identified, for a per procedure incidence of 0.39%. The vertebral artery was the most commonly dissected vessel (49/68, 72%). 67 of 68 cases (98.5%) were managed conservatively with either no treatment or medical therapy alone. There were two adverse events potentially attributable to the dissections, only one of which was symptomatic.

Conclusions

Iatrogenic dissections occur infrequently during cerebral angiography. When dissections do occur, most cases can be safely managed without further intervention in the acute setting.
Optimizing endovascular stroke treatment: removing the microcatheter before clot retrieval with stent-retrievers increases aspiration flow
Authors: Nikoubashman Omid , Alt Jan Patrick , Nikoubashman Arash , Büsen Martin , Heringer Sarah , Brockmann Carolin , Brockmann Marc-Alexander , Müller Marguerite , Reich Arno , Wiesmann Martin
Published: April 2016

Background

Flow control during endovascular stroke treatment with stent-retrievers is crucial for successful revascularization. The standard technique recommended by stent-retriever manufacturers implies obstruction of the respective access catheter by the microcatheter, through which the stent-retriever is delivered. This, in turn, results in reduced aspiration during thrombectomy. In order to maximize aspiration, we fully retract the microcatheter out of the access catheter before thrombectomy—an approach we term the ‘bare wire thrombectomy’ (BWT) technique. We verified the improved throughput with systematic in vitro studies and assessed the clinical effectiveness and safety of this method.

Methods

We compared aspiration flow of water through various access catheters (5–8 F) with a Rebar microcatheter (0.18 inch and 0.27 inch) and a Trevo stent-retriever using the standard technique and the BWT technique in vitro. We also retrospectively analyzed 302 retrieval maneuvers in 117 patients who received endovascular treatment with a stent-retriever between February 2010 and April 2015.

Results

In the in vitro experiment, removal of the microcatheter in all tested settings resulted in significantly increased aspiration flow through the access catheter (p<0.001). This effect was particularly pronounced in access catheters with a diameter of ≤7 F. In the clinical study, the revascularization rate (Thrombolysis In Cerebral Infarction ≥2b) was 91%. There were no complications associated with the BWT technique in 302 retrieval maneuvers.

Conclusions

The BWT technique results in improved aspiration flow rates compared with the standard deployment technique. Our clinical data show that the BWT technique is effective and safe.
Timeline of blood pressure changes after intra-arterial therapy for acute ischemic stroke based on recanalization status
Authors: John Seby , Hazaa Walaa , Uchino Ken , Hussain Muhammad S
Published: April 2016

Background

There is sparse literature on the natural history of blood pressure (BP) after intra-arterial therapy (IAT) for acute ischemic stroke (AIS).

Methods

A retrospective analysis was performed of patients with AIS who underwent IAT without endotracheal intubation for internal carotid artery terminus (ICA-T) or M1 middle cerebral artery occlusion from January 2008 to February 2012. Systolic BP (SBP) values at the beginning (First) and end (End) of IAT and for 36 h after the procedure were collected. Successful recanalization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b–3.

Results

Sixty-two patients (14 (22.5%) ICA-T, 46 (74.2%) M1, 2 (3.2%) ICA-T+M1) met the study criteria and 37 (59.7%) achieved successful recanalization. The First and End SBP values were similar in the successful (Group R) and unsuccessful (Group NR) recanalization groups. Taking the whole cohort, End SBP was significantly lower than First SBP, but this decline was significant only in Group R. Subsequently, absolute SBP values in Group R were not significantly different from Group NR. However, when comparing the hourly decline of SBP with First SBP, Group R demonstrated a greater fall than Group NR and the decline was significantly different from hours 8 to 12 post-procedure. The SBP in Group NR then decreased further, and its difference from baseline was similar to Group R from hour 14 onwards. Mean SBP and SBP variability over 36 h were similar between the two groups.

Conclusions

SBP falls significantly in patients with AIS with large vessel occlusion who recanalize with IAT. While SBP in non-recanalized patients also drops from baseline, it occurs to a lesser degree and stays higher only for a short period of time before falling to similar levels as in recanalized patients.
Effect of dual pulmonary vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease: a retrospective analysis
Authors: Monfredi Oliver , Heward Elliot , Griffiths Linda , Condliffe Robin , Mahadevan Vaikom S
Published: April 2016

Background

Patients with pulmonary arterial hypertension (PAH) are managed according to evidence-based treatment guidelines.

Methods and results

In this single-centre retrospective analysis, we examined outcomes of patients with PAH caused by congenital heart disease (PAH-CHD) with respect to exercise capacity and survival of adults treated with either bosentan or sildenafil monotherapy or bosentan-sildenafil dual therapy between January 2007 and January 2014. Of the 82 patients analysed, 29 had Down syndrome; 54 (65.8%) received bosentan monotherapy, 16 (19.5%) sildenafil monotherapy and 12 (14.6%) dual therapy. Mean treatment duration was 2.5 years for all patients and 4.1 years for 38 patients treated for ≥2 years. Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD). For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy. Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3-year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively.

Conclusions

For the majority of patients, monotherapy with a PAH-specific medication provided improved and sustained exercise benefits. For the small percentage of patients who required it, add-on therapy appeared to prevent further deterioration in exercise capacity but did not improve 6MWD.
Evaluation of a workshop to improve residents' patient-centred obesity counselling skills
Authors: Burton Amy M , Brezausek Carl M , Agne April A , Hankins Shirley L , Willett Lisa L , Cherrington Andrea L
Published: April 2016

Background

Primary care physicians are being asked to counsel their patients on obesity and weight management. Few physicians conduct weight loss counselling citing barriers, among them a lack of training and confidence. Our objective was to pilot test the effectiveness of a 3-h interactive obesity-counselling workshop for resident physicians based on motivational interviewing (MI) techniques.

Design

This study used a pretest/post-test cross-sectional design. A convenience sample of resident physicians was invited to participate. Participating resident physicians completed a preintervention and postintervention questionnaire to assess their knowledge, beliefs and confidence in obesity counselling. MI techniques taught in the intervention were evaluated by audio recording interviews with a standardised patient (SP) pre intervention and post intervention. Audio recordings were transcribed and coded by two independent coders using a validated assessment tool. Paired t tests were used to assess preintervention and postintervention differences.

Results

Eight-six residents attended the workshop. At baseline, the majority (71%) felt that there is not enough time to counsel patients about obesity and only 24% felt that residency trained them to counsel. After the intervention, knowledge and confidence in counselling increased (p<0.001). Among the 55 residents with complete pre-post SP interview data, MI adherent statements increased from a mean of 2.88 to 5.42 while the MI non-adherent statements decreased from 6.73 to 2.33 (p<0.001).

Conclusions

After a brief workshop to train physicians to counsel on obesity-related behaviours, residents improved their counselling skills and felt more confident on counselling patients. Future studies are needed to assess whether these gains are sustained over time.
Pestivirus in alpine wild ruminants and sympatric livestock from the Cantabrian Mountains, Spain
Authors: Fernández‐Aguilar X. , López‐Olvera J. R. , Marco I. , Rosell R. , Colom‐Cadena A. , Soto‐Heras S. , Lavín S. , Cabezón O.
Published: April 2016

Bovine viral diarrhoea virus (BVDV) and Border disease virus (BDV) were investigated at the wildlife‐livestock interface in the distribution area of chamois in the Cantabrian Mountains, North‐Western Spain. From 2010 to 2014, sera from sympatric wild (n=167) and domestic (n=272) ruminants were analysed for pestivirus antibodies by cELISA, virus neutralisation test (VNT) and for the presence of pestiviral RNA using a reverse transcription (RT)‐PCR. Results showed a higher seroprevalence in cattle (59.4 per cent, 13/13 of herds) than in domestic small ruminants (5.9 per cent sheep, 2/8 of flocks; 0 per cent goats of 4 flocks) and wildlife (10.8 per cent in red deer, 0 per cent in roe deer and 0 per cent in Cantabrian chamois). High VNT titres were detected in two cattle herds, suggesting the circulation of BVDV‐1 and BVDV‐2 strains. BVDV‐1 RNA was detected in one cattle calf by RT‐PCR and sequencing. Conversely to other similar grazing systems, sheep flocks did not play a relevant role in the pestivirus epidemiology in this region. Pestivirus infections in wild ruminants were sporadic and most probably dependent on a domestic source.
Anaesthesia with sevoflurane in pigeons: minimal anaesthetic concentration (MAC) determination and investigation of cardiorespiratory variables at 1 MAC
Authors: Botman J. , Gabriel F. , Dugdale A. H. A. , Vandeweerd J.‐M.
Published: April 2016

The objective of the study was to determine the minimal anaesthetic concentration (MAC) of sevoflurane (SEVO) in pigeons and investigate the effects of 1 MAC SEVO anaesthesia on cardiovascular and respiratory variables compared with the awake state. This is a prospective, experimental study. Animals were seven healthy adult pigeons. After acclimatisation to handling, heart rate (HR), heart rhythm, respiratory rate (f R), end‐expired carbon dioxide tension (PE′CO2), inspired CO2 tension, indirect systolic arterial blood pressure (SAP) and cloacal temperature were measured to determine baseline, ‘awake’ values. Pigeons were then anaesthetised with SEVO and MAC was determined by the ‘bracketing’ method. The same variables were monitored during a 40 minute period at 1.0 MAC SEVO for each bird. Mean MAC was 3.0±0.6 per cent for SEVO. During maintenance of anaesthesia at 1.0 MAC, SAP decreased significantly (P<0.001) without any significant change in HR. Although PE′CO2 increased significantly (P=0.001) despite an increase in f R, awake PE′CO2 values were unexpectedly low. Sinus arrhythmias were detected in two birds under SEVO anaesthesia. The times to tracheal intubation and to recovery were 2.5±0.7 and 6.4±1.7 minutes, respectively. Recovery was rapid and uneventful in all birds. In conclusion, SEVO is suitable for anaesthesia in pigeons.
Prescribed burning of harvested boreal black spruce forests in eastern Canada: effect on understory vegetation
Authors: Faivre Nicolas , Boudreault Catherine , Renard Sébastien , Fenton Nicole J. , Gauthier Sylvie , Bergeron Yves
Published: April 2016

Ecosystem-based management advocates that forestry disturbances should aim to emulate natural disturbances to mitigate the landscape-level impact of forest management. This study compares the impact of clear-cuts followed by a prescribed burn (CCPB) with clear-cuts alone (CC) and current careful logging practices (CLAAG: “careful logging around advanced growth”) on understory composition within black spruce (Picea mariana Miller (BSP)) paludified forest stands at the plot, site, and treatment levels using a functional-type approach. Vascular and nonvascular taxa showed significant differences in composition at the plot level among treatments. We found that pioneer taxa occurred mainly in CCPB sites, while late-successional taxa characterized CC sites. CLAAG sites had higher taxa richness than CCPB and CC sites, and we found that CCPB treatments were most likely to promote vascular taxa compositions that are more similar to those observed after natural disturbances. Additionally, the relative abundance of Sphagnum spp., responsible for paludification, was significantly reduced in sites treated by prescribed burning. This study therefore presents results suggesting that prescribed burning might represent a sustainable alternative to current harvesting techniques in the Clay Belt of eastern Canada that could help in preserving biodiversity (in terms of understory species assemblage) while maintaining or even enhancing forest productivity.
Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats
Authors: Caravan Ionut , Sevastre Berghian Alexandra , Moldovan Remus , Decea Nicoleta , Orasan Remus , Filip Gabriela Adriana
Published: April 2016

Menopause is accompanied by enhanced oxidative stress and behavioral changes, effects attenuated by antioxidants. The aim of this study was to evaluate the effects of caffeine on behavior and oxidative stress in an experimental model of menopause. Female rats were divided into the following groups: sham-operated (CON), sham-operated and caffeine-treated (CAF), ovariectomized (OVX), ovariectomized and caffeine-treated (OVX+CAF). Caffeine (6 mg/kg) and vehicle were administered for 21 days (subchronic) and 42 days (chronic), using 2 experimental subsets. Behavioral tests and oxidative stress parameters in the blood, whole brain, and hippocampus were assessed. The subchronic administration of caffeine decreased the lipid peroxidation and improved the antioxidant defense in the blood and brain. The GSH/GGSG ratio in the brain was improved by chronic administration, with reduced activities of antioxidant enzymes and enhanced nitric oxide and malondialdehyde levels. In particular, the lipid peroxidation in the hippocampus decreased in both experiments. The rats became hyperactive after 21 days of treatment, but no effect was observed after chronic administration. In both experimental subsets, caffeine had anxiolytic effects as tested in elevated plus maze. The administration of low doses of caffeine, for a short period of time, may be a new therapeutic approach to modulating the oxidative stress and anxiety in menopause.
Spring-tillage has no effect on the emergence pattern of glyphosate-resistant giant ragweed (Ambrosia trifida L.) in Nebraska
Authors: Kaur Simranpreet , Werle Rodrigo , Sandell Lowell , Jhala Amit J.
Published: April 2016

The objective of this study was to investigate the effect of spring tillage on glyphosate-resistant giant ragweed emergence pattern. Giant ragweed emerged from late Mar. until early June and tillage had no effect on total seedling emergence and days required to reach 50% cumulative emergence (T50); however, results differed between years.
Performance analysis of optical micro-ring resonator as all-optical reconfigurable logic and multiplexer in Z-domain
Authors: Verma Nidhi , Mandal Sanjoy
Published: April 2016

Performance and design methodology of [Formula: see text] multiplexer (MUX) and all-optical reconfigurable logic circuit using GaAs–AlGaAs-based optical micro-ring resonator (OMRR) are presented in current paper. Proposed design of reconfigurable logic circuit is capable to perform eight different logic operations. Performances of the logic circuits have been theoretically analyzed using Z-domain modeling. Numerical simulation results confirming the method are explained in the present paper. Proposed circuit is simple, compact, efficient as it have minimum number of OMRR, low operating power, high operating speed and high Q-factor. Different ‘figure of merits’ of the purposed model are calculated from the simulation results.
Greenhouse to icehouse: a biostratigraphic review of latest Devonian–Mississippian glaciations and their global effects
Authors: Lakin J. A. , Marshall J. E. A. , Troth I. , Harding I. C.
Published: April 2016

The latest Devonian–Mississippian interval records the long-term transition from Devonian greenhouse conditions into the Late Palaeozoic Ice Age (LPIA). This transition was punctuated by three short glaciation events in the latest Famennian, mid-Tournaisian and Visean stages, respectively. Primary evidence for glaciation is based on diamictite deposits and striated pavements in South America, Appalachia and Africa. The aim of this review is to assess the primary biostratigraphic and sedimentological data constraining diamictite deposits through this transition. These data are then compared to the wider record of eustasy, mass extinction and isotope stratigraphy in the lower palaeolatitudes. Precise age determinations are vital to integrate high- and low-palaeolatitude datasets, and to understand the glacial control on wider global changes. Palynological techniques currently provide the best biostratigraphic tool to date these glacial deposits and to correlate the effects of glaciation globally. This review highlights a high degree of uncertainty in the known history of early LPIA glaciation as much of the primary stratigraphic data are limited and/or unpublished. Future high-resolution stratigraphic studies are needed to constrain the history of glaciation both spatially and temporally through the latest Devonian and Mississippian.
Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease
Authors: Ohlmeier Steffen , Nieminen Pentti , Gao Jing , Kanerva Tinja , Rönty Mikko , Toljamo Tuula , Bergmann Ulrich , Mazur Witold , Pulkkinen Ville
Published: April 2016

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by irreversible airflow limitation. Cigarette smoking represents the main risk factor, but the specific mechanisms of COPD are not completely understood. Our aim was to identify COPD-specific proteomic changes involved in disease onset and severity. A comparative proteomic analysis of 51 lung tissues from nonsmokers, smokers, smokers with mild to moderate (stage I–II) COPD, severe to very severe COPD (stage III–IV), and patients with α-1-antitrypsin deficiency (AATD) and idiopathic pulmonary fibrosis (IPF) was performed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Selected COPD-specific changes were validated by immunoblotting and further by ELISA in 120 induced sputum and plasma samples from nonsmokers, smokers, and patients with COPD (stage I–III). Altogether 82 altered proteins were identified comprising COPD-, AATD-, and IPF-specific, overlapping, and unspecific changes. Cathepsin D (CTSD), dihydropyrimidinase-related protein 2 (DPYSL2), transglutaminase 2 (TGM2), and tripeptidyl-peptidase 1 (TPP1) were validated as COPD-specific. TGM2 was not associated with smoking and correlated with COPD severity in lung tissue. TGM2 levels in sputum and plasma were elevated in patients with COPD (stage II–III) and correlated with lung function. In conclusion, new proteins related to COPD onset and severity could be identified with TGM2 being a novel potential diagnostic and therapeutic target for COPD. Further studies in carefully characterized cohorts are required to validate the identified changes.
The TLR7 agonist imiquimod induces bronchodilation via a nonneuronal TLR7-independent mechanism: a possible role for quinoline in airway dilation
Authors: Larsson Olivia J. , Manson Martijn L. , Starkhammar Magnus , Fuchs Barbara , Adner Mikael , Kumlien Georén Susanna , Cardell Lars-Olaf
Published: April 2016

Toll-like receptor (TLR) 7 agonists are known to reduce allergic airway inflammation. Their recently reported ability to rapidly relax airways has further increased their interest in the treatment of pulmonary disease. However, the mechanisms behind this effect are not fully understood. The present study, therefore, aimed to determine whether airway smooth muscle (ASM)-dependent mechanisms could be identified. TLR7 agonists were added to guinea pig airways following precontraction with carbachol in vitro or histamine in vivo. Pharmacological inhibitors were used to dissect conventional pathways of bronchodilation; tetrodotoxin was used or bilateral vagotomy was performed to assess neuronal involvement. Human ASM cells (HASMCs) were employed to determine the effect of TLR7 agonists on intracellular Ca2+([Ca2+]i) mobilization. The well-established TLR7 agonist imiquimod rapidly relaxed precontracted airways in vitro and in vivo. This relaxation was demonstrated to be independent of nitric oxide, carbon monoxide, and cAMP signaling, as well as neuronal activity. A limited role for prostanoids could be detected. Imiquimod induced [Ca2+]irelease from endoplasmic reticulum stores in HASMCs, inhibiting histamine-induced [Ca2+]i. The TLR7 antagonist IRS661 failed to inhibit relaxation, and the structurally dissimilar agonist CL264 did not relax airways or inhibit [Ca2+]i. This study shows that imiquimod acts directly on ASM to induce bronchorelaxation, via a TLR7-independent release of [Ca2+]i. The effect is paralleled by other bronchorelaxant compounds, like chloroquine, which, like imiquimod, but unlike CL264, contains the chemical structure quinoline. Compounds with quinoline moieties may be of interest in the development of multifunctional drugs to treat pulmonary disease.
Lipoxin A4prevents tight junction disruption and delays the colonization of cystic fibrosis bronchial epithelial cells byPseudomonas aeruginosa
Authors: Higgins Gerard , Fustero Torre Coral , Tyrrell Jean , McNally Paul , Harvey Brian J. , Urbach Valerie
Published: April 2016

The specialized proresolution lipid mediator lipoxin A4(LXA4) is abnormally produced in cystic fibrosis (CF) airways. LXA4increases the CF airway surface liquid height and stimulates airway epithelial repair and tight junction formation. We report here a protective effect of LXA4(1 nM) against tight junction disruption caused by Pseudomonas aeruginosa bacterial challenge together with a delaying action against bacterial invasion in CF airway epithelial cells from patients with CF and immortalized cell lines. Bacterial invasion and tight junction integrity were measured by gentamicin exclusion assays and confocal fluorescence microscopy in non-CF (NuLi-1) and CF (CuFi-1) bronchial epithelial cell lines and in primary CF cultures, grown under an air/liquid interface, exposed to either a clinical or laboratory strains of P. aeruginosa. LXA4delayed P. aeruginosa invasion and transepithelial migration in CF and normal bronchial epithelial cell cultures. These protective effects of LXA4were inhibited by the ALX/FPR2 lipoxin receptor antagonist BOC-2. LXA4prevented the reduction in mRNA biosynthesis and protein abundance of the tight junction protein ZO-1 and reduced tight junction disruption induced by P. aeruginsosa inoculation. In conclusion, LXA4plays a protective role in bronchial epithelium by stimulating tight junction repair and by delaying and reducing the invasion of CF bronchial epithelial cells by P. aeruginsosa.
Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?
Authors: Cai Bin , Luo Yu-long , Wang Shi-jun , Wei Wei-yuan , Zhang Xue-hui , Huang Wei , Li Tong , Zhang Meng , Wu Nan , Roodrajeetsing Gopaul , Zhang Sen
Published: April 2016

Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1βwere significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.
The Variational Homotopy Perturbation Method for Solving((n×n)+1)Dimensional Burgers’ Equations
Authors: Hendi F. A. , Kashkari B. S. , Alderremy A. A.
Published: April 2016

The variational homotopy perturbation method VHPM is used for solvingn-dimensional Burgers’ system. Some examples are examined to validate that the method reduced the calculation size, treating the difficulty of nonlinear term and the accuracy.
Differences in Knowledge, Attitude, and Behavior towards HIV/AIDS and Sexually Transmitted Infections between Sexually Active Foreign and Chinese Medical Students
Authors: Kuete Martin , Huang Qiao , Rashid Abid , Ma Xiu Lan , Yuan HongFang , Escalera Antezana Juan Pablo , Yeltay Rakhmanov , Rao Meng , He Qian , Xiong ChengLiang , Zhang HuiPing
Published: April 2016

Although the prevalence of human immunodeficiency virus (HIV) decreased in the last decade worldwide, the number of deaths due to HIV/AIDS and communicable diseases including syphilis, hepatitis, and tuberculosis had dramatically increased in developing countries. Education and behavior are incredibly important factors to prevent these diseases’ spread. This study highlights the range of differences in knowledge, attitude, and behavior of 434 sexually active medical students towards HIV/AIDS and sexually transmitted infections (STIs). Because the surveyed population constitutes the forefront of healthcare providers and was originated from different area of the world, this is the first time a study sought to investigate the behavioral attitude of this group of population irrespective of the three levels of their academic and professional knowledge. Several factors including sociodemographic characteristics, sexual behavior, HIV/AIDS, and STIs related patterns play a key role in medical student attitude and behavior towards people infected with HIV/AIDS and STIs. Our findings add consistent value in prior studies which aimed to stop new infections and also imply further investigations on the management of the studied infections by medical students. The present study arouses much interest among participants and provides evidence of reinforcing medical students’ education on HIV/AIDS and STIs.
Online Knowledge-Based Model for Big Data Topic Extraction
Authors: Khan Muhammad Taimoor , Durrani Mehr , Khalid Shehzad , Aziz Furqan
Published: April 2016

Lifelong machine learning (LML) models learn with experience maintaining a knowledge-base, without user intervention. Unlike traditional single-domain models they can easily scale up to explore big data. The existing LML models have high data dependency, consume more resources, and do not support streaming data. This paper proposes online LML model (OAMC) to support streaming data with reduced data dependency. With engineering the knowledge-base and introducing new knowledge features the learning pattern of the model is improved for data arriving in pieces. OAMC improves accuracy as topic coherence by 7% for streaming data while reducing the processing cost to half.
Modulation of Drug Resistance inStaphylococcus aureuswith Coumarin Derivatives
Authors: de Araújo Rodrigo Santos Aquino , Barbosa-Filho José Maria , Scotti Marcus Tullius , Scotti Luciana , Cruz Ryldene Marques Duarte da , Falcão-Silva Vivyanne dos Santos , Siqueira-Júnior José Pinto de , Mendonça-Junior Francisco Jaime Bezerra
Published: April 2016

Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistantStaphylococcus aureusas based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistantS. aureusstrains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that18is a potential ligand presenting lowEbinding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition inS. aureus.
Herpes Simplex Virus-2 Esophagitis in a Young Immunocompetent Adult
Authors: Kadayakkara Deepak K. , Candelaria Angela , Kwak Ye Eun , Loeser Caroline
Published: April 2016

Herpes simplex esophagitis (HSE) is commonly identified in immunosuppressed patients. It is rare among immunocompetent patients and almost all of the reported cases are due to HSV-1 infection. HSV-2 esophagitis is extremely rare. We report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. Endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. However, classic histopathological findings of multinucleated giant cells with eosinophilic intranuclear inclusions and positive HSV-2 IgM confirmed the diagnosis of HSV-2 esophagitis. The patient rapidly responded to acyclovir treatment. Although HSV-2 is predominantly associated with genital herpes, it can cause infections in other parts of the body previously attributed to only HSV-1 infection.
miR-339-3p Is a Tumor Suppressor in Melanoma
Authors: Weber Claudia E.M. , Luo Chonglin , Hotz-Wagenblatt Agnes , Gardyan Adriane , Kordaß Theresa , Holland-Letz Tim , Osen Wolfram , Eichmüller Stefan B.
Published: April 2016

Determinants of invasion and metastasis in cancer remain of great interest to define. Here, we report the definition of miR-339-3p as a novel tumor suppressive microRNA that blocks melanoma cell invasion without affecting cell survival. miR-339-3p was identified by a comprehensive functional screen of a human miRNA mimetic library in a cell-based assay for invasion by the melanoma cell line A375. miR-339-3p was determined as a strong inhibitor of invasion differentially expressed in melanoma cells and healthy melanocytes. MCL1 was defined as a target for downregulation by miR-339-3p, functioning through direct interaction with the 3′ untranslated region of MCL1 mRNA. Blocking miR-339-3p by an antagomiR was sufficient to increase melanoma cell invasion, an effect that could be phenocopied by RNAi-mediated silencing of MCL1. In vivo studies established that miR-339-3p overexpression was sufficient to decrease lung colonization by A375 melanoma cells in NSG mice, relative to control cells. Overall, our results defined miR-339-3p as a melanoma tumor suppressor, the levels of which contributes to invasive aggressiveness. Cancer Res; 76(12); 3562–71. ©2016 AACR.
Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP
Authors: Hatzl Stefan , Geiger Olivia , Kuepper Maja Kim , Caraffini Veronica , Seime Till , Furlan Tobias , Nussbaumer Erika , Wieser Rotraud , Pichler Martin , Scheideler Marcel , Nowek Katarzyna , Jongen-Lavrencic Mojca , Quehenberger Franz , Wölfler Albert , Troppmair Jakob , Sill Heinz , Zebisch Armin
Published: April 2016

RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of miRNAs within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By using an RKIP 3′-untranslated region luciferase reporter construct with and without mutation or deletion of the putative miR-23a–binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a–binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4,300 primary patient specimens via database retrieval from The Cancer Genome Atlas, we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity. Cancer Res; 76(12); 3644–54. ©2016 AACR.
The Role of PGC1α in Cancer Metabolism and its Therapeutic Implications
Authors: Tan Zheqiong , Luo Xiangjian , Xiao Lanbo , Tang Min , Bode Ann M. , Dong Zigang , Cao Ya
Published: April 2016

PGC1α is a transcription factor coactivator that influences a majority of cellular metabolic pathways. Abnormal expression of PGC1α is associated with several chronic diseases and, in recent years, it has been shown to be a critical controller of cancer development. PGC1α acts as a stress sensor in cancer cells and can be activated by nutrient deprivation, oxidative damage, and chemotherapy. It influences mitochondria respiration, reactive oxygen species defense system, and fatty acid metabolism by interacting with specific transcription factors. The characteristic traits of PGC1α in maintaining metabolic homeostasis promote cancer cell survival and tumor metastasis in harsh microenvironments. Not only does PGC1α act as a coactivator, but is also itself controlled by oncogenes and transcription factors. PGC1α and these molecules can form signaling axes that include PML/PGC1α/PPARα, MITF/PGC1α, and PGC1α/ERRα, which are important in regulating metabolic adaptation in specific cancer types. Some of these PGC1α-associated pathways are inherently activated in cancer cells, and others are induced by stress, which enable cancer cells to acquire resistance against therapy. Notably, certain therapeutic-resistant cancer cells are addicted to PGC1α-dependent metabolic activities. Suppression of PGC1α expression resensitizes these cells to therapeutic treatments, which implicates PGC1α as a promising target in cancer molecular classification and therapy. Mol Cancer Ther; 15(5); 774–82. ©2016 AACR.
Dysregulation of WNT5A/ROR2 Signaling Characterizes the Progression of Barrett-Associated Esophageal Adenocarcinoma
Authors: Lyros Orestis , Nie Linghui , Moore Tami , Medda Rituparna , Otterson Mary , Behmaram Behnaz , Mackinnon Alexander , Gockel Ines , Shaker Reza , Rafiee Parvaneh
Published: April 2016

The mechanism underlying the progression of normal esophageal mucosa to esophageal adenocarcinoma remains elusive. WNT5A is a noncanonical WNT, which mainly functions via the receptor tyrosine kinase-like orphan receptor 2 (ROR2), and has an unclear role in carcinogenesis. In this study, we aimed to determine the role of WNT5A/ROR2 signaling in esophageal adenocarcinoma. Analysis of WNT5A and ROR2 expression patterns in healthy controls, Barrett and esophageal adenocarcinoma patients' esophageal clinical specimens as well as in various esophageal cell lines demonstrated a ROR2 overexpression in esophageal adenocarcinoma tissues compared with Barrett and healthy mucosa, whereas WNT5A expression was found significantly downregulated toward esophageal adenocarcinoma formation. Treatment of esophageal adenocarcinoma OE33 cells with human recombinant WNT5A (rhWNT5A) significantly suppressed proliferation, survival, and migration in a dose-dependent fashion. rhWNT5A was found to inhibit TOPflash activity in ROR2 wild-type cells, whereas increased TOPflash activity in ROR2-knockdown OE33 cells. In addition, ROR2 knockdown alone abolished cell proliferation and weakened the migration properties of OE33 cells. These findings support an early dysregulation of the noncanonical WNT5A/ROR2 pathway in the pathogenesis of esophageal adenocarcinoma, with the loss of WNT5A expression together with the ROR2 overexpression to be consistent with tumor promotion.

Implications: The dysregulation of WNT5A/ROR2 noncanonical WNT signaling in Barrett-associated esophageal adenocarcinoma introduces possible prognostic markers and novel targets for tailored therapy of this malignancy. Mol Cancer Res; 14(7); 647–59. ©2016 AACR.
Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial–Mesenchymal Transition: Effects on Anoikis
Authors: Farris Joshua C. , Pifer Phillip M. , Zheng Liang , Gottlieb Eyal , Denvir James , Frisch Steven M.
Published: April 2016

Resistance to anoikis is a prerequisite for tumor metastasis. The epithelial-to-mesenchymal transition (EMT) allows tumor cells to evade anoikis. The wound-healing regulatory transcription factor Grainyhead-like 2 (GRHL2) suppresses/reverses EMT, accompanied by suppression of the cancer stem cell (CSC) phenotype and by resensitization to anoikis. Here, the effects of GRHL2 upon intracellular metabolism in the context of reversion of the EMT/CSC phenotype, with a view toward understanding how these effects promote anoikis sensitivity, were investigated. EMT enhanced mitochondrial oxidative metabolism. Although this was accompanied by higher accumulation of superoxide, the overall level of reactive oxygen species (ROS) declined, due to decreased hydrogen peroxide. Glutamate dehydrogenase 1 (GLUD1) expression increased in EMT, and this increase, via the product α-ketoglutarate (α-KG), was important for suppressing hydrogen peroxide and protecting against anoikis. GRHL2 suppressed GLUD1 gene expression, decreased α-KG, increased ROS, and sensitized cells to anoikis.

Implications: These results demonstrate a mechanistic role for GRHL2 in promoting anoikis through metabolic alterations. Mol Cancer Res; 14(6); 528–38. ©2016 AACR.
Captive Conditions of Pet Lemurs in Madagascar
Authors: Reuter Kim E. , Schaefer Melissa S.
Published: April 2016

Live extraction of wildlife is a threat to biodiversity and can compromise animal welfare standards. Studies of the captive environments and welfare of pet primates are known, but none has focused on Madagascar. We aimed to expand knowledge about the captive conditions of pet lemurs in Madagascar. We hypothesized that captive lemurs would often be kept in restrictive settings, including small cages, would be fed foods inconsistent with their natural diets and, as a result, would be in bad physical or psychological health. Data were collected via a web-based survey (n = 253 reports) and from the websites and social media pages of 25 hotels. Most lemurs seen by respondents were either kept on a rope/leash/chain or in a cage (67%), though some lemurs were habituated and were not restrained (28%). Most of the time (72%) cages were considered small, and lemurs were rarely kept in captivity together with other lemurs (81% of lemurs were caged alone). Pet lemurs were often fed foods inconsistent with their natural diets, and most (53%) were described as being in bad health. These findings point to a need to undertake outreach to pet lemur owners in Madagascar about the captivity requirements of primates.
Two Patients with Dry Eye Disease Followed Up Using an Expression Assay of Ocular Surface Mucin
Authors: Machida Yumiko , Shoji Jun , Harada Natsuko , Inada Noriko
Published: April 2016

Purpose: We report 2 patients with dry eye disease followed up using the expression levels of ocular surface mucin. Case Reports: Patient 1: a 57-year-old woman with Sjögren's syndrome-associated dry eyes experienced severe dryness and foreign body sensation in both her eyes, and instilled sodium hyaluronate ophthalmic solution 0.3% about 10-15 times daily. We measured the expression levels of MUC5AC mRNA (MUC5AC) and MUC16 mRNA (MUC16) by using real-time reversed transcription polymerase chain reaction for the specimens of modified impression cytology. Expression levels of MUC5AC and MUC16 on her ocular surface were very low. Subjective symptoms and expression levels of ocular surface mucin improved after combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Patient 2: a 62-year-old man with chronic graft-versus-host disease-associated dry eye experienced severe foreign body sensation and developed superficial punctate keratopathy with mucous thread and filamentary keratitis. Expression level of MUC5AC was very high at baseline. Subjective symptoms and expression levels of ocular surface mucin improved by combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Conclusion: Clinical test for MUC gene expression on the ocular surface was found to be useful in the follow-up of dry eye treatment.
A Second Case of Gobello Nevus Syndrome
Authors: Tadini Gianluca , Rossi Luisa Carlotta , Faure Elisa , Besagni Francesca , Boneschi Vinicio , Esposito Susanna , Brena Michela
Published: April 2016

An uncommon type of epidermal nevus characterized by hyperpigmented hyperkeratotic bands following a Blaschko-linear pattern and generalized follicular hyperkeratosis were observed in a 17-year-old male patient who additionally showed tufted hair folliculitis on the scalp and clinodactyly of the fifth finger of both hands. The combination of epidermal nevus with skeletal abnormalities was first described by Gobello et al. [Dermatology 2000;201:51-55] as a new epidermal nevus syndrome that was named after the first author of this work. Our case shows identical clinical and histopathological features and represents the second case of this rare syndrome reported in the literature.