bluuebunny/crossref_metadata_2025 huggingface dataset:
Misinterpretation of the Borg’s Rating of Perceived Exertion Scale by patients with panic disorder during ergospirometry challenge
Authors: Muotri Ricardo William , Bernik Marcio Antonini , Neto Francisco Lotufo
Published: April 2017

Introduction

The most widely used instrument to measure perceived exertion or exercise intensity is the Borg’s Rating of Perceived Exertion (RPE) Scale. Panic attacks are aversive experiences that may be triggered by bodily sensations such as palpitations, breathlessness or dizziness due to increasing autonomic distress, prior sensitisation to panic and fear conditioning. The consequence is catastrophic interpretation of bodily sensations of arousal in general, which can lead to misinterpretation of exertion or exercise intensity.

Purpose

To verify the effectiveness of the Borg’s RPE Scale as a measure of perceived effort in panic disorder subjects.

Methods

The study enrolled 72 subjects: the control group (C, healthy sedentary subjects, n=30) and patients with panic disorder (PD, n=42). All subjects were submitted to an ergospirometry challenge. Perceived exertion RPE scores and heart rate at 90% VO2max were compared between groups.

Results

Patients with PD showed lower levels of maximal oxygen consumption, when compared with C group [VO2max (mL/kg/min): PD=29.42±6.50xC=34.51±5.35; Student's t-test=−3.51; p <0.05]. Furthermore, among PD subjects, the maximum heart rate during ergospirometry challenge was lower than expected [predict max HR (bpm)=200.85±6.33xheart rate test (bpm)=178.86±7.28; Z=−5.64; p<0.05]. Perceived exertion, as measured by RPE, was also overestimated in relation to heart rate at 90% of maximum oxygen consumption compared with controls (RPE90%VO2max: PD=18.93±0.55xC=16.67±0.60; U=8.00; Z=7.42; p<0.05).

Conclusions

The present study findings suggest that the Borg’s RPE Scale may not be an appropriate measure of subjective exertion among subjects with panic disorder performing a cardiopulmonary exercise test.
The Casper carotid artery stent: a unique all metal micromesh stent designed to prevent embolic release
Authors: Diaz Orlando , Lopez Gloria , Roehm John O F , De la Rosa Ginna , Orozco Fernando , Almeida Rafael
Published: April 2017

Background

Stroke due to the release of embolic debris during the placement of a stent to correct carotid artery stenosis is a constant procedural and peri-procedural threat. The new all metal Casper stent has been created with two layers of nitinol, the inner layer of which has pores diminutive enough to prevent embolic release.

Objective

To evaluate the safety, effectiveness, and utility of the double layer nitinol Casper carotid artery stent in the treatment of patients with severe carotid artery stenosis.

Methods

19 patients with severe internal carotid artery stenosis, 14 symptomatic and 5 asymptomatic, were treated with the Casper stent. After stent placement, angiographic and cone beam CT images were recorded in all patients.

Results

The unique low profile delivery system allowed for easy stent placement, re-sheathing, and repositioning of the stent. The large cell external layer produced excellent apposition to the artery wall. The inner layer prevented prolapse of atherosclerotic debris through the device. Plaque coverage was achieved; residual stenosis ranged from 0% to 20%. Long term angiographic follow-up in 5 patients showed wall apposition of the device covering the lesion and no restenosis. There were no procedure related complications. Two patients experienced a delayed ischemic stroke, likely related to inconsistent medical management.

Conclusions

The Casper has been an excellent stent for the treatment of internal carotid artery stenosis and its internal micromesh layer has been effective in preventing plaque prolapse. It provides the flexibility of large cell stents and the inner layer provides maximum protection against plaque prolapse.
Production of glandular trichomes responds to water stress and temperature in silver birch (Betula pendula) leaves
Authors: Thitz P. , Possen B.J.H.M. , Oksanen E. , Mehtätalo L. , Virjamo V. , Vapaavuori E.
Published: April 2017

Silver birch (Betula pendula Roth) allocates substantial resources to the production of glandular trichomes. If these trichomes can protect trees from temperature and water stress, their production would be expected to increase under these conditions. We studied how glandular trichome density and number in the leaves of two-year-old silver birch plantlets respond to single and combined treatments of elevated temperature (+1 °C) and three different levels of soil moisture (low, normal, and excess watering). Moreover, we quantified the seasonal variation in trichome density in mature long-shoot leaves of young, greenhouse-grown silver birches. Our results demonstrate clear differences between responses of glandular trichomes on different leaf surfaces. On the adaxial leaf surface, both drought and elevated temperature reduced the production of glandular trichomes. Interestingly, this response was absent in plants subjected to the combined treatment. Glandular trichome production on the abaxial leaf surface increased considerably in leaves produced during the growing season, reflecting a seasonal trend. Maintaining a strong seasonal increase in trichome production of abaxial surfaces even in low-water conditions suggests an important, though still unknown, role for abaxial glandular trichomes. In silver birch stems, those trichomes are strongly responsible for herbivore defense.
Dark matter reflection of particle symmetry
Authors: Khlopov Maxim Yu.
Published: April 2017

In the context of the relationship between physics of cosmological dark matter and symmetry of elementary particles, a wide list of dark matter candidates is possible. New symmetries provide stability of different new particles and their combination can lead to a multicomponent dark matter. The pattern of symmetry breaking involves phase transitions in the very early Universe, extending the list of candidates by topological defects and even primordial nonlinear structures.
(In)dependence of 𝜃 in the Higgs regime without axions
Authors: Shifman Mikhail , Vainshtein Arkady
Published: April 2017

We revisit the issue of the vacuum angle [Formula: see text] dependence in weakly coupled (Higgsed) Yang–Mills theories. Two most popular mechanisms for eliminating physical [Formula: see text] dependence are massless quarks and axions. Anselm and Johansen noted that the vacuum angle [Formula: see text], associated with the electroweak SU(2) in the Glashow–Weinberg–Salam model (Standard Model, SM), is unobservable although all fermion fields obtain masses through Higgsing and there is no axion. We generalize this idea to a broad class of Higgsed Yang–Mills theories.

In the second part, we consider the consequences of Grand Unification. We start from a unifying group, e.g. SU(5), at a high ultraviolet scale and evolve the theory down within the Wilson procedure. If on the way to infrared the unifying group is broken down into a few factors, all factor groups inherit one and the same [Formula: see text] angle — that of the unifying group. We show that embedding the SM in SU(5) drastically changes the Anselm–Johansen conclusion: the electroweak vacuum angle [Formula: see text], equal to [Formula: see text] becomes in principle observable in [Formula: see text] processes. We also note in passing that if the axion mechanism is set up above the unification scale, we have one and the same axion in the electroweak theory and QCD, and their impacts are interdependent.
Elastic scattering and spatial inelastic profiles of high energy protons
Authors: Dremin I. M.
Published: April 2017

The ratio of elastic to total proton cross-sections is related to the darkness of the spatial profile of inelastic interactions by a single parameter in the framework of a simple analytical model. Their critical values at LHC energies are discussed. Two possible variants of their asymptotical behavior are described.
Effect of composition on the tensile properties and fracture toughness of A7N01S-T5 aluminum alloys welded joints
Authors: Liu Yali , Gou Guoqing , Chen Jia , Chen Hui , Wang Wanjng , Li Xiaodong , Che Xiaoli , Wang Yirong
Published: April 2017

In this paper, welded joints of four types of A7N01S-T5 aluminum alloy with different chemical compositions were investigated. The welding process was under 70% environmental humidity conditions at 10[Formula: see text]C with single-pulse GMAW welding technology. The strength and fracture toughness of the four types of samples were tested, and the microstructures were investigated by micro-X-ray fluorescence (SR-LXRF) technology and backscattered electron diffraction (EBSD) technology. The results showed that the #2 alloy that is composed of Zn: 4.59 wt.%, Mg: 1.56 wt.% Mn: 0.22 wt.%, Cr: 0.14 wt.%, Zr: 0.01 wt.% and Ti: 0.027 wt.% had the best combination of tensile strength and elongation, with the values of 302.35 MPa and 3.74%, respectively. The better result for the combination of the strength and elongation was mainly determined by the volume fraction and size. The fine grain size and compositions played important roles to obtain high fracture toughness.
Influence of sintering process on electrical properties and PTCR effect of laminated Ba1.005(Ti1−xNbx)O3 ceramics fired in a reducing atmosphere
Authors: Cheng Xuxin , Li Xiaoxia , Chen Xiaoming , Cui Haining
Published: April 2017

This study investigates the influence of dopant content and firing conditions on electrical properties and positive temperature coefficient of resistance (PTCR) effect of Ba[Formula: see text](Ti[Formula: see text]Nb[Formula: see text]O3 (BTN) ceramics sintered at different temperatures from 1070[Formula: see text]C to 1220[Formula: see text]C for 2 h in a reducing atmosphere and reoxidized within the temperature range of 600[Formula: see text]–[Formula: see text]750[Formula: see text]C for 0.5[Formula: see text]–[Formula: see text]8 h. The results indicate that the room-temperature (RT) resistance of the laminated BTN specimens initially decreased and then increased as a function of the dopant concentration. Moreover, the resistance jump exhibited a contrasting tendency. Furthermore, the RT resistance of the BTN samples rapidly decreased at first and then gradually decreased with increasing sintering temperature. Meanwhile, the resistance jump of the samples increased first and then decreased. In addition, the influence of reoxidation times on the PTCR characteristics of ceramics was investigated.
On the existence of min-max minimal surface of genus g ≥ 2
Authors: Zhou Xin
Published: April 2017

In this paper, we establish a min-max theory for minimal surfaces using sweepouts of surfaces of genus [Formula: see text]. We develop a direct variational method similar to the proof of the famous Plateau problem by Douglas [Solution of the problem of Plateau, Trans. Amer. Math. Soc. 33 (1931) 263–321] and Rado [On Plateau’s problem, Ann. Math. 31 (1930) 457–469]. As a result, we show that the min-max value for the area functional can be achieved by a bubble tree limit consisting of branched genus-[Formula: see text] minimal surfaces with nodes, and possibly finitely many branched minimal spheres. We also prove a Colding–Minicozzi type strong convergence theorem similar to the classical mountain pass lemma. Our results extend the min-max theory by Colding–Minicozzi and the author to all genera.
Least energy solutions for indefinite biharmonic problems via modified Nehari–Pankov manifold
Authors: Niu Miaomiao , Tang Zhongwei , Wang Lushun
Published: April 2017

In this paper, by using a modified Nehari–Pankov manifold, we prove the existence and the asymptotic behavior of least energy solutions for the following indefinite biharmonic equation: [Formula: see text] where [Formula: see text], [Formula: see text], [Formula: see text] is a parameter, [Formula: see text] is a nonnegative potential function with nonempty zero set [Formula: see text], [Formula: see text] is a positive function such that the operator [Formula: see text] is indefinite and non-degenerate for [Formula: see text] large. We show that both in subcritical and critical cases, equation [Formula: see text] admits a least energy solution which for [Formula: see text] large localized near the zero set [Formula: see text].
Climate Change Adaptation Pathways in Kolkata
Authors: Parasuram Priya , Narayanan Priya , Pelling Mark , Solecki William , Ramachandran Purvaja , Ramachandran Ramesh
Published: April 2017

Disaster risk management and wider processes of adaptation are too often understood in isolation from development. Kolkata faces increasing heatwaves, flood hazard and everyday waterlogging as a result of climate change but the social and spatial distribution of impacts will likely be mediated by historic and contemporary development decisions. The paper reports on a study that has combined a scenario workshop method and expert interviews to surface the views of risk and resilience planners, academics and urban professionals on the adaptation–development nexus. Kolkata is experiencing rapid and fundamental transition in its governance regimes and economic structures as state-led development gives way to stronger market forces. Planners welcome an opening of urban governance but are worried by the speed of change. Transition in risk governance is observed in a predicted shift from a contemporary orientation where capacity is limited but focused on protecting development gains, to one which also embraces the flexibility of resilience.
Nerve Growth Factor and Pain Mechanisms
Authors: Denk Franziska , Bennett David L. , McMahon Stephen B.
Published: April 2017

Nerve growth factor (NGF) antagonism is on the verge of becoming a powerful analgesic treatment for numerous conditions, including osteoarthritis and lower back pain. This review summarizes the historical research, both fundamental and clinical, that led to our current understanding of NGF biology. We also discuss the surprising number of questions that remain about NGF expression patterns and NGF's various functions and interaction partners in relation to persistent pain and the potential side effects of anti-NGF therapy.
Inhibition of cholinergic neurotransmission by β3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders
Authors: Silva Isabel , Costa Ana Filipa , Moreira Sílvia , Ferreirinha Fátima , Magalhães-Cardoso Maria Teresa , Calejo Isabel , Silva-Ramos Miguel , Correia-de-Sá Paulo
Published: April 2017

The direct detrusor relaxant effect of β3-adrenoceptor agonists as a primary mechanism to improve overactive bladder symptoms has been questioned. Among other targets, activation of β3-adrenoceptors downmodulate nerve-evoked acetylcholine (ACh) release, but there is insufficient evidence for the presence of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a retrograde messenger via prejunctional A1receptors to explain inhibition of cholinergic activity by β3-adrenoceptors. Isoprenaline (1 µM) decreased [3H]ACh release from stimulated (10 Hz, 200 pulses) human (−47 ± 5%) and rat (−38 ± 1%) detrusor strips. Mirabegron (0.1 µM, −53 ± 8%) and CL316,243 (1 µM, −37 ± 7%) mimicked isoprenaline (1 µM) inhibition, and their effects were prevented by blocking β3-adrenoceptors with L748,337 (30 nM) and SR59230A (100 nM), respectively, in human and rat detrusor. Mirabegron and isoprenaline increased extracellular adenosine in the detrusor. Blockage of A1receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM) or the equilibrative nucleoside transporters (ENT) with dipyridamole (0.5 µM) prevented mirabegron and isoprenaline inhibitory effects. Dipyridamole prevented isoprenaline-induced adenosine outflow from the rat detrusor, and this effect was mimicked by the ENT1 inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI, 30 µM). Cystometry recordings in anesthetized rats demonstrated that SR59230A, DPCPX, dipyridamole, and NBTI reversed the decrease in the voiding frequency caused by isoprenaline (0.1–1,000 nM). Data suggest that inhibition of cholinergic neurotransmission by β3-adrenoceptors results from adenosine release via equilibrative nucleoside transporters and prejunctional A1-receptor stimulation in human and rat urinary bladder.
Impaired popliteal artery flow-mediated dilation caused by reduced daily physical activity is prevented by increased shear stress
Authors: Teixeira André L. , Padilla Jaume , Vianna Lauro C.
Published: April 2017

We recently showed that 5 days of reduced daily physical activity impair popliteal artery, but not brachial artery, flow-mediated dilation (FMD). However, the mechanisms by which physical inactivity causes leg vascular dysfunction are unclear. We reason that a reduction in leg blood flow-induced shear stress is a primary underlying mechanism by which reduced daily physical activity impairs popliteal artery FMD. Thus the purpose of this study was to determine whether increased leg blood flow and shear stress during inactivity prevent the reduction in popliteal artery FMD. Bilateral popliteal artery FMD measures were performed at baseline and after 5 days of a transition from high (>10,000 steps/day) to low levels (<5,000 steps/day) of physical activity in 13 healthy and physically active men [20 ± 2 (SD) yr]. During the inactive period, one foot was submerged in ~42°C water (i.e., heated leg) three times a day for 30 min each period, to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated leg). During heating, popliteal artery mean shear rate was increased in the heated leg (change of 119.3 ± 26.4%, P < 0.01) but slightly decreased in the nonheated leg (change of −21.8 ± 7.5%, P = 0.03). Popliteal artery FMD was impaired after 5 days of reduced daily physical activity in the control nonheated leg ( P < 0.01) but was unchanged in the heated leg ( P = 0.34). These results support the hypothesis that reduced leg blood flow-induced shear stress during physical inactivity is a key underlying mechanism mediating leg vascular dysfunction.

NEW & NOTEWORTHY We found that the impairment in popliteal artery flow-mediated dilation caused by physical inactivity can be prevented by increased shear stress. These findings indicate that reduced leg blood flow-induced shear stress during physical inactivity may be a key underlying mechanism mediating the detrimental leg vascular effects of physical inactivity. Heating the foot area may be used as a nonpharmacological therapy to combat inactivity-induced leg vascular dysfunction, especially in people who are unable or unwilling to be active.
A Distributed Tactile Sensor for Intuitive Human-Robot Interfacing
Authors: Cirillo Andrea , Cirillo Pasquale , De Maria Giuseppe , Natale Ciro , Pirozzi Salvatore
Published: April 2017

Safety of human-robot physical interaction is enabled not only by suitable robot control strategies but also by suitable sensing technologies. For example, if distributed tactile sensors were available on the robot, they could be used not only to detect unintentional collisions, but also as human-machine interface by enabling a new mode of social interaction with the machine. Starting from their previous works, the authors developed a conformable distributed tactile sensor that can be easily conformed to the different parts of the robot body. Its ability to estimate contact force components and to provide a tactile map with an accurate spatial resolution enables the robot to handle both unintentional collisions in safe human-robot collaboration tasks and intentional touches where the sensor is used as human-machine interface. In this paper, the authors present the characterization of the proposed tactile sensor and they show how it can be also exploited to recognize haptic tactile gestures, by tailoring recognition algorithms, well known in the image processing field, to the case of tactile images. In particular, a set of haptic gestures has been defined to test three recognition algorithms on a group of 20 users. The paper demonstrates how the same sensor originally designed to manage unintentional collisions can be successfully used also as human-machine interface.
Depression Treatment among Adults with Multiple Sclerosis and Depression in Ambulatory Care Settings in the United States
Authors: Bhattacharjee Sandipan , Goldstone Lisa , Ip Queeny , Warholak Terri
Published: April 2017

Background. There is little information regarding depression treatment patterns among adults with MS and depression in ambulatory settings at national level in the United States (US).Objectives. The objectives of this study were to identify patterns and predictors of depression treatment in ambulatory settings in US among adults with MS and depression.Methods. A cross-sectional study was conducted by pooling multiple years (2005–2011) of National Ambulatory Medical Care Survey and the outpatient department of the National Hospital Ambulatory Medical Care Survey data. The final study sample was comprised of ambulatory visits among adults with MS and depression. Dependent variable of this study was pharmacological treatment for depression with or without psychotherapy. Predictors of depression treatment were determined by conducting multivariable logistic regression.Results. Out of all ambulatory visits involving MS diagnosis, 20.59% also involved a depression diagnosis. Depression treatment was observed in 57.25% of the study population. Fluoxetine was the most prescribed individual antidepressant. Age and total number of chronic diseases were significant predictors of depression treatment.Conclusion. Approximately six out of ten ambulatory visits involving MS and depression recorded some form of depression treatment. Future longitudinal studies should examine health outcomes associated with depression treatment in this population.
Andiroba Oil (Carapa guianensis Aublet) Nanoemulsions: Development and Assessment of Cytotoxicity, Genotoxicity, and Hematotoxicity
Authors: Milhomem-Paixão Susana Suely Rodrigues , Fascineli Maria Luiza , Muehlmann Luis Alexandre , Melo Karina Motta , Salgado Hugo Leonardo Crisóstomo , Joanitti Graziella Anselmo , Pieczarka Julio Cesar , Azevedo Ricardo Bentes , Santos Alberdan Silva , Grisolia Cesar Koppe
Published: April 2017

Andiroba oil (AO) is obtained from an Amazonian plant and is used in traditional medicine. We carried out a comparative study to test the cytotoxicity, genotoxicity, and hematotoxicity of the oil and its nanoemulsion (AN) in vitro (fibroblasts, lineage NIH/3T3) and in vivo (Swiss mice). The AN was characterized by DLS/Zeta, and its stability was investigated for 120 days. The biological activity of AN was assessed in vitro by MTT test and cell morphology analyses and in vivo by micronucleus, comet, and hematotoxicity tests. The AN presented a hydrodynamic diameter (Hd) of 142.5±3.0 and PDI of 0.272±0.007 and good stability at room temperature. The MTT test evidenced the cytotoxicity of AO and of AN only at their highest concentrations, but AN showed lower cytotoxicity than AO. A lower cytotoxicity of AN, when compared to AO, is in fact an interesting data suggesting that during therapeutic application there will be a lower impact in the cell viability of healthy cells. Cytotoxicity, genotoxicity, and hematotoxicity were not observed in vivo. These tests on the biological and toxicological effects of andiroba oil and nanostructured oil are still initial ones but will give a direction to future application in cosmetics and/or the development of new phytotherapics.
Understanding the Connection between Cognitive Impairment and Mobility: What Can Be Gained from Neuropsychological Assessment?
Authors: Pavol Marykay A. , Stein Joel , Kabir Foyruz M. , Yip Jonathan , Sorkin Lyssa Y. , Marshall Randolph S. , Lazar Ronald M.
Published: April 2017

The ability of neuropsychological tests to predict rehabilitation outcome is unclear, particularly when other ratings of cognition are available. Neuropsychological test scores and functional ratings of cognition (Functional Independence Measure (FIM) Cognition score) were used to predict improvement in patient mobility and self-care skill, as measured by the FIM Motor score. Regression models used both raw neuropsychology test scores and age-adjusted scores. Retrospective chart review was performed for patients on an inpatient rehabilitation unit and referred for neuropsychological assessment. The group included 126 subjects (average age 64.2 ± 17.1 years) and a variety of medical diagnoses. Neuropsychological tests included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). After forcing the Admission FIM Cognition score into the model, RBANS scores and duration of rehabilitation predicted FIM Motor improvements (F=11.42,p<0.0001). Raw neuropsychological test scores performed better than the model with age-adjusted test scores. FIM Cognition alone did not predict FIM Motor improvements. Neuropsychological tests, combined with duration of rehabilitation, predicted mobility gains for patients undergoing inpatient rehabilitation beyond what was predicted by another, readily available, assessment of cognition. Neuropsychology raw scores performed better than age-adjusted scores, raising questions about the standard use of demographic adjustments for predicting real-world function.
Reconfigurable Antenna Arrays with Multiple Requirements: A Versatile 3D Approach
Authors: Comisso Massimiliano , Buttazzoni Giulia , Vescovo Roberto
Published: April 2017

This paper proposes a deterministic method for the 3D synthesis of antenna arrays that jointly accounts for far-field pattern reconfigurability, polarization setting, dynamic range ratio reduction, and near-field control. The conceived algorithm, which generalizes some existing solutions, relies on a weighted cost function, whose iterative minimization is accomplished by properly derived closed-form expressions. This feature, combined with the possibility of selecting the weighting parameters, provides a fast and versatile approach, whose capabilities are numerically checked by considering different synthesis problems and array structures in the presence of mutual coupling.
Endotracheal Intubation Using a Direct Laryngoscope and the Protective Performances of Respirators: A Randomized Trial
Authors: Lim Taeho , Lee Sanghyun , Oh Jaehoon , Kang Hyunggoo , Ahn Chiwon , Song Yeongtak , Lee Juncheol , Shin Hyungoo
Published: April 2017

Purpose. Emergency physicians are at risk for infection during invasive procedures, and the respirators can reduce this risk. This study aimed to determine whether endotracheal intubation using direct laryngoscopes affected protection performances of respirators. Methods. A randomized crossover study of 24 emergency physicians was performed. We performed quantitative fit tests using respirators (cup type, fold type without a valve, and fold type with a valve) before and during intubation. The primary outcome was respirators’ fit factors (FF), and secondary outcomes were acceptable protection (percentage of scores above 100 FF [FF%]). Results. 24 pieces of data were analyzed. Compared to fold-type respirator without a valve, FF and FF% values were lower when participants wore a cup-type respirator (200 FF [200-200] versus 200 FF [102.75–200], 100% [78.61–100] versus 74.16% [36.1–98.9]; all P<0.05) or fold-type respirator with a valve (200 FF [200-200] versus 142.5 FF [63.50–200], 100% [76.10–100] versus 62.50% [8.13–100]; all P<0.05). There were no significant differences in intubation time and success rate according to respirator types. Conclusions. Motion during endotracheal intubation using direct laryngoscopes influenced the protective performance of some respirators. Therefore, emergency physicians should identify and wear respirators that provide the best personalized fit for intended tasks.
In VitroEvaluations andIn VivoToxicity and Efficacy Studies of MFM501 against MRSA
Authors: Johari Saiful Azmi , Mohtar Mastura , Syed Mohamad Sharifah Aminah , Mohammat Mohd Fazli , Sahdan Rohana , Mohamed Azman , Mohamad Ridhwan Mohamad Jemain
Published: April 2017

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis,in vivooral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.
Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity
Authors: Seth Pankaj , Csizmadia Eva , Hedblom Andreas , Vuerich Marta , Xie Han , Li Mailin , Longhi Maria Serena , Wegiel Barbara
Published: April 2017

Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis, diminished numbers of PD-L1+ cancer cells, increased numbers of CD3+ T cells, and activation status of CD8+ T cells. Furthermore, it was associated with more pronounced antitumor T-cell immunity via induction of IL17 and IFNγ-producing CD8+ T (Tc17 and Tc1) cells, likely via suppression of lactate-driven PD-L1 expression. Our results suggest that expressions of LDH-A and lactate by macrophage in the tumor microenvironment are major drivers of T-cell immunosuppression, strongly supporting the concept of targeting stromal LDH-A as an effective strategy to blunt tumoral immune escape. Cancer Res; 77(13); 3632–43. ©2017 AACR.
The Epigenetic Regulation of GATA4-Dependent Brain Natriuretic Peptide Expression during Alcohol Withdrawal
Authors: Glahn Alexander , Rhein Mathias , Heberlein Annemarie , Muschler Marc , Kornhuber Johannes , Frieling Helge , Bleich Stefan , Hillemacher Thomas
Published: April 2017

Objective: Natriuretic peptides participate in the collection of metabolic effects during alcohol withdrawal. Having witnessed modulation of other natriuretic peptides in alcohol-dependent patients during alcohol withdrawal, we were interested in the relation of brain natriuretic peptide (BNP) methylation with protein expression and craving in this longitudinal study. Methods: Ninety-nine male patients were compared to 101 healthy controls concerning epigenetic regulation and protein expression during detoxification treatment. Results: With BNP expression being GATA4 dependent, we observed a correlation of GATA4 binding site methylation and protein expression. BNP serum levels and Obsessive Compulsive Drinking Scale scores are significantly decreased during withdrawal. Focusing on the two CpGs that are between GATA transcription factor binding sites, statistical analysis revealed a reversely proportional methylation pattern, significantly increasing with ongoing detoxification and thereby supporting the observed serum level changes. Conclusion: Without the functional knowledge about regulation of BNP expression via the GATA transcription factor, it would have been easy to take the mean results of the global CpG data and propose a direct relationship between methylation and expression. Thus, these findings are a voice for functionally and mechanistically approved results. There was no causal relationship between protein expression levels and epigenetic changes. Further research is needed which includes protein expression and other approaches.
Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum
Authors: McDougall Annie R.A. , Wiradjaja Vanny , Azhan Aminath , Li Anqi , Hale Nadia , Wlodek Mary E. , Hooper Stuart B. , Wallace Megan J. , Tolcos Mary
Published: April 2017

Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR.
Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia Associated with Dementia with Lewy Bodies: A Pilot Study
Authors: Lapid Maria I. , Kuntz Karen M. , Mason Sara S. , Aakre Jeremiah A. , Lundt Emily S. , Kremers Walter , Allen Laura A. , Drubach Daniel A. , Boeve Bradley F.
Published: April 2017

Background/Aims: Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. Methods: We performed a 12-week pilot trial of armodafinil therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The patients underwent neurologic examinations, a neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks. Safety assessment included laboratory examinations, QTc interval, and heart rate. Tolerability was assessed by analysis of adverse events. Data were analyzed using the last-observation-carried-forward method. Results: Of 20 participants, 17 completed the protocol. The median age was 72 years, most of the participants were men (80%), and most had spouses as caregivers. The Epworth Sleepiness Scale (p < 0.001), Maintenance of Wakefulness Test (p = 0.003), and Clinical Global Impression of Change (p < 0.001) scores improved at week 12. The Neuropsychiatric Inventory total score (p = 0.003), visual hallucinations (p = 0.003), and agitation (p = 0.02) improved at week 4. Caregiver overall quality of life improved at week 12 (p = 0.004). No adverse events occurred. Conclusion: These pilot data suggest improvements in hypersomnia and wakefulness and reasonable safety and tolerability of armodafinil therapy in hypersomnolent patients with DLB. Our findings inform the use of pharmacologic strategies for managing hypersomnolence in these patients.
Testicular Metastasis from Renal Cell Carcinoma: A Case Report and Review of the Literature
Authors: Rouvinov Keren , Neulander Endre Z. , Kan Elena , Asali Murad , Ariad Samuel , Mermershtain Wilmosh
Published: April 2017

Testicular metastases from renal cell carcinoma (RCC) are extremely rare. To the best of our knowledge, only 33 cases have been described in the literature. Most of the reported cases are of unilateral testicular metastasis from RCC. We report a case of metachronous ipsilateral testicular metastasis from RCC in a 78-year-old man 6 years after nephrectomy. Scrotal ultrasonography showed a 4 × 5 cm mass in the right testis. Right inguinal orchiectomy was performed for diagnosis. Computed tomography revealed liver and lung metastases. First-line therapy with sunitinib was started in November 2016 for metastatic RCC.
Crucial Role of ROCK2-Mediated Phosphorylation and Upregulation of FHOD3 in the Pathogenesis of Angiotensin II–Induced Cardiac Hypertrophy
Authors: Zhou Qing , Wei Si-Si , Wang Hong , Wang Qian , Li Wei , Li Gang , Hou Jian-Wen , Chen Xiao-Meng , Chen Jie , Xu Wei-Ping , Li Yi-Gang , Wang Yue-Peng
Published: April 2017

Cardiac hypertrophy is characterized by increased myofibrillogenesis. Angiotensin II (Ang-II) is an essential mediator of the pressure overload–induced cardiac hypertrophy in part through RhoA/ROCK (small GTPase/Rho-associated coiled-coil containing protein kinase) pathway. FHOD3 (formin homology 2 domain containing 3), a cardiac-restricted member of diaphanous-related formins, is crucial in regulating myofibrillogenesis in cardiomyocytes. FHOD3 maintains inactive through autoinhibition by an intramolecular interaction between its C- and N-terminal domains. Phosphorylation of the 3 highly conserved residues (1406S, 1412S, and 1416T) within the C terminus (CT) of FHOD3 by ROCK1 is sufficient for its activation. However, it is unclear whether ROCK-mediated FHOD3 activation plays a role in the pathogenesis of Ang-II–induced cardiac hypertrophy. In this study, we detected increases in FHOD3 expression and phosphorylation in cardiomyocytes from Ang-II–induced rat cardiac hypertrophy models. Valsartan attenuated such increases. In cultured neonate rat cardiomyocytes, overexpression of phosphor-mimetic mutant FHOD3-DDD, but not wild-type FHOD3, resulted in myofibrillogenesis and cardiomyocyte hypertrophy. Expression of a phosphor-resistant mutant FHOD3-AAA completely abolished myofibrillogenesis and attenuated Ang-II–induced cardiomyocyte hypertrophy. Pretreatment of neonate rat cardiomyocytes with ROCK inhibitor Y27632 reduced Ang-II–induced FHOD3 activation and upregulation, suggesting the involvement of ROCK activities. Silencing of ROCK2, but not ROCK1, in neonate rat cardiomyocytes, significantly lessened Ang-II–induced cardiomyocyte hypertrophy. ROCK2 can directly phosphorylate FHOD3 at both 1412S and 1416T in vitro and is more potent than ROCK1. Both kinases failed to phosphorylate 1406S. Coexpression of FHOD3 with constitutively active ROCK2 induced more stress fiber formation than that with constitutively active ROCK1. Collectively, our results demonstrated the importance of ROCK2 regulated FHOD3 expression and activation in Ang-II–induced myofibrillogenesis, thus provided a novel mechanism for the pathogenesis of Ang-II–induced cardiac hypertrophy.
Seasonal Variability in Warm-Water Inflow toward Kangerdlugssuaq Fjord
Authors: Gelderloos Renske , Haine Thomas W. N. , Koszalka Inga M. , Magaldi Marcello G.
Published: April 2017

Seasonal variability in pathways of warm-water masses toward the Kangerdlugssuaq Fjord (KF)–Glacier (KG) system, southeast Greenland, is investigated by backtracking Lagrangian particles seeded at the fjord mouth in a high-resolution regional ocean model simulation in the ice-free and the ice-covered seasons. The waters at KF are a mixture of Atlantic-origin water advected from the Irminger Basin [Faxaflói (FF)], the deep waters from the Denmark Strait, and the waters from the Arctic Ocean, both represented by the Kögur section (KO). Below 200-m depth, the warm water is a mixture of FF and KO water masses and is warmer in winter than in summer. The authors find that seasonal differences in pathways double the fraction of FF particles in winter, causing the seasonal warming and salinification. Seasonal temperature variations at the upstream sections (FF and KO) have a negligible impact on temperature variations near the fjord. Successful monitoring of heat flux to the fjord therefore needs to take place close to the fjord and cannot be inferred from upstream conditions.
Frontal Circulation and Submesoscale Variability during the Formation of a Southern Ocean Mesoscale Eddy
Authors: Adams Katherine A. , Hosegood Philip , Taylor John R. , Sallée Jean-Baptiste , Bachman Scott , Torres Ricardo , Stamper Megan
Published: April 2017

Observations made in the Scotia Sea during the May 2015 Surface Mixed Layer Evolution at Submesoscales (SMILES) research cruise captured submesoscale, O(1–10) km, variability along the periphery of a mesoscale O(10–100) km meander precisely as it separated from the Antarctic Circumpolar Current (ACC) and formed a cyclonic eddy ~120 km in diameter. The meander developed in the Scotia Sea, an eddy-rich region east of the Drake Passage where the Subantarctic and Polar Fronts converge and modifications of Subantarctic Mode Water (SAMW) occur. In situ measurements reveal a rich submesoscale structure of temperature and salinity and a loss of frontal integrity along the newly formed southern sector of the eddy. A mathematical framework is developed to estimate vertical velocity from collocated drifter and horizontal water velocity time series, under certain simplifying assumptions appropriate for the current dataset. Upwelling (downwelling) rates of O(100) m day−1 are found in the northern (southern) eddy sector. Favorable conditions for submesoscale instabilities are found in the mixed layer, particularly at the beginning of the survey in the vicinity of density fronts. Shallower mixed layer depths and increased stratification are observed later in the survey on the inner edge of the front. Evolution in temperature–salinity (T–S) space indicates modification of water mass properties in the upper 200 m over 2 days. Modifications along σθ = 27–27.2 kg m−3 have climate-related implications for mode and intermediate water transformation in the Scotia Sea on finer spatiotemporal scales than observed previously.
Analyzing Simulated Convective Bursts in Two Atlantic Hurricanes. Part I: Burst Formation and Development
Authors: Hazelton Andrew T. , Rogers Robert F. , Hart Robert E.
Published: April 2017

Understanding the structure and evolution of the tropical cyclone (TC) inner core remains an elusive challenge in tropical meteorology, especially the role of transient asymmetric features such as localized strong updrafts known as convective bursts (CBs). This study investigates the formation of CBs and their role in TC structure and evolution using high-resolution simulations of two Atlantic hurricanes (Dean in 2007 and Bill in 2009) with the Weather Research and Forecasting (WRF) Model.

Several different aspects of the dynamics and thermodynamics of the TC inner-core region are investigated with respect to their influence on TC convective burst development. Composites with CBs show stronger radial inflow in the lowest 2 km, and stronger radial outflow from the eye to the eyewall around z = 2–4 km, than composites without CBs. Asymmetric vorticity associated with eyewall mesovortices appears to be a major factor in some of the radial flow anomalies that lead to CB development. The anomalous outflow from these mesovortices, along with outflow from supergradient parcels above the boundary layer, favors low-level convergence and also appears to mix high-θe air from the eye into the eyewall. Analyses of individual CBs and parcel trajectories show that parcels are pulled into the eye and briefly mix with the eye air. The parcels then rapidly move outward into the eyewall, and quickly ascend in CBs, in some cases with vertical velocities of over 20 m s−1. These results support the importance of horizontal asymmetries in forcing extreme asymmetric vertical velocity in tropical cyclones.
Does Student Loan Debt Deter Higher Education Participation? New Evidence from England
Authors: Callender Claire , Mason Geoff
Published: April 2017

Research among prospective UK undergraduates in 2002 found that some students, especially from low social classes, were deterred from applying to university because of fear of debt. This article investigates whether this is still the case today in England despite the changing higher education landscape since 2002. The article describes findings from a 2015 survey of prospective undergraduates and compares them with those from the 2002 study. We find that students’ attitudes to taking on student loan debt are more favorable in 2015 than in 2002. Debt-averse attitudes remain much stronger among lower-class students than among upper-class students, and more so than in 2002. However, lower-class students in 2015 do not have stronger debt-averse attitudes than do middle-class students. Finally, debt-averse attitudes seem more likely to deter planning for higher education among lower-class students in 2015 than in 2002.
Learn Now, Pay Later: A History of Income-Contingent Student Loans in the United States
Authors: Shireman Robert
Published: April 2017

The idea of financing higher education with the income that comes afterward has been formally proposed and implemented in the United States, in various permutations, since at least 1971. The attractiveness of the concept is exemplified by the political diversity of its proponents, ranging from Senator Ted Kennedy to President Ronald Reagan, and from presidential candidates Michael Dukakis (Democratic governor who ran in 1988) to Jeb Bush (Republican former governor who ran in 2016). This article examines the design of the various proposals over time, the arguments in support and opposition, and the current state of affairs.
Institutional Accountability: A Comparison of the Predictors of Student Loan Repayment and Default Rates
Authors: Kelchen Robert , Li Amy Y.
Published: April 2017

The federal government holds colleges accountable if too many of their students default on loan repayment, but the default measure traditionally used captures only a fraction of students who are struggling to repay their loans. The 2015 College Scorecard dataset introduced a new loan repayment metric, showing that the percentage of students who have not reduced the principal balance of their loans by at least $1 over a given period of time far outstrips the traditional loan default measure. Using a sample of 3,595 colleges, we test the extent to which student demographics, institutional characteristics, and state-level economic factors are associated with repayment rates and default rates. We also examine whether factors associated with loan repayment rates change between one and seven years after students begin repayment. We find that characteristics traditionally associated with economic disadvantage, including being a first-generation college student or a member of an underrepresented minority group, tend to be associated with lower loan repayment rates, as does attendance at for-profit colleges. These factors are just as or more strongly associated with longer-term repayment rates compared to shorter-term repayment rates.