bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms and New Strategies for Primary Sjögren's Syndrome
Authors: Mavragani Clio P.
Published: January 2017

Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development. Activation of both innate and adaptive immune pathways contributes to disease pathogenesis, with prominent interferon (IFN) signatures identified in both peripheral blood and affected salivary gland tissues. Recently, LINE-1 genomic repeat elements have been proposed as potential triggers of type I IFN pathway activation in SS through activation of Toll-like receptor–dependent and –independent pathways. In view of the increasingly appreciated variability of SS, elucidation of distinct operating pathways in relation to diverse clinical phenotypes and selection of the optimal therapeutic intervention remain major challenges. Inhibition of cathepsin S molecules, blockade of costimulation through administration of abatacept and inhibitors of B7-related molecules and CD40, blockade of B cell function and B cell survival factors, and disruption of the formation of ectopic germinal centers are considered the main therapeutic targets. Well-controlled multicenter clinical trials are ongoing and data are awaited.
Lymphangioleiomyomatosis: A Monogenic Model of Malignancy
Authors: Krymskaya Vera P. , McCormack Francis X.
Published: January 2017

Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure. Dysregulated cellular signaling results in a shift from oxidative phosphorylation to glycolysis as the preferred mode of energy generation, to allow for the accumulation of biomass required for cell growth and tolerance of nutrient-poor, anaerobic environments. Symptomatic LAM occurs almost exclusively in females after menarche, highlighting the central but as yet poorly understood role for sex-restricted anatomical structures and/or hormones in disease pathogenesis. LAM is an elegant model of malignancy because biallelic mutations at a single genetic locus confer all features that define cancer upon the LAM cell—metabolic reprogramming and proliferative signals that drive uncontrolled growth and inappropriate migration and invasion, the capacity to exploit the lymphatic circulation as a vehicle for metastasis and access to the lungs, and destruction of remote tissues. The direct benefit of the study of this rare disease has been the rapid identification of an effective FDA-approved therapy, and the collateral benefits have included elucidation of the pivotal roles of mTOR signaling in the regulation of cellular metabolism and the pathogenesis of cancer.
Correlation between discharge timings of pairs of motor units reveals the presence but not the proportion of common synaptic input to motor neurons
Authors: Rodriguez-Falces Javier , Negro Francesco , Farina Dario
Published: January 2017

We investigated whether correlation measures derived from pairs of motor unit (MU) spike trains are reliable indicators of the degree of common synaptic input to motor neurons. Several 50-s isometric contractions of the biceps brachii muscle were performed at different target forces ranging from 10 to 30% of the maximal voluntary contraction relying on force feedback. Forty-eight pairs of MUs were examined at various force levels. Motor unit synchrony was assessed by cross-correlation analysis using three indexes: the output correlation as the peak of the cross-histogram (ρ) and the number of synchronous spikes per second (CIS) and per trigger (E). Individual analysis of MU pairs revealed that ρ, CIS, and E were most often positively associated with discharge rate (87, 85, and 76% of the MU pairs, respectively) and negatively with interspike interval variability (69, 65, and 62% of the MU pairs, respectively). Moreover, the behavior of synchronization indexes with discharge rate (and interspike interval variability) varied greatly among the MU pairs. These results were consistent with theoretical predictions, which showed that the output correlation between pairs of spike trains depends on the statistics of the input current and motor neuron intrinsic properties that differ for different motor neuron pairs. In conclusion, the synchronization between MU firing trains is necessarily caused by the (functional) common input to motor neurons, but it is not possible to infer the degree of shared common input to a pair of motor neurons on the basis of correlation measures of their output spike trains.

NEW & NOTEWORTHY The strength of correlation between output spike trains is only poorly associated with the degree of common input to the population of motor neurons. The synchronization between motor unit firing trains is necessarily caused by the (functional) common input to motor neurons, but it is not possible to infer the degree of shared common input to a pair of motor neurons on the basis of correlation measures of their output spike trains.
Nitriding Process Characterization of Cold Worked AISI 304 and 316 Austenitic Stainless Steels
Authors: Monteiro Waldemar Alfredo , Pereira Silvio Andre Lima , Vatavuk Jan
Published: January 2017

The nitriding behavior of austenitic stainless steels (AISI 304 and 316) was studied by different cold work degree (0% (after heat treated), 10%, 20%, 30%, and 40%) before nitride processing. The microstructure, layer thickness, hardness, and chemical microcomposition were evaluated employing optical microscopy, Vickers hardness, and scanning electron microscopy techniques (WDS microanalysis). The initial cold work (previous plastic deformations) in both AISI 304 and 306 austenitic stainless steels does not show special influence in all applied nitriding kinetics (in layer thicknesses). The nitriding processes have formed two layers, one external layer formed by expanded austenite with high nitrogen content, followed by another thinner layer just below formed by expanded austenite with a high presence of carbon (back diffusion). An enhanced diffusion can be observed on AISI 304 steel comparing with AISI 316 steel (a nitrided layer thicker can be noticed in the AISI 304 steel). The mechanical strength of both steels after nitriding processes reveals significant hardness values, almost 1100 HV, on the nitrided layers.
Abundance and Significance of Neuroligin-1 and Neurexin II in the Enteric Nervous System of Embryonic Rats
Authors: Wang Dongming , Pan Jingnian , Song Guoxin , Gao Ni , Zheng Yi , Zhang Qiangye , Li Aiwu
Published: January 2017

Aim. To investigate the abundance of neuroligin-1 and neurexin II in the enteric nervous system (ENS) of rats on different embryonic days and to explore their potential significance.Methods. The full-thickness colon specimens proximal to the ileocecal junction of rats on embryonic days 16, 18, and 20 and of newborns within 24 hours (E16, E18, E20, and Ep0) were studied, respectively. qRT-PCR was applied for detecting the expressions of neuroligin-1 and neurexin II on mRNA, and western blotting was employed for detecting their further expressions on the whole tissue. Finally, the histological appearance of neuroligin-1 and neurexin IIαwas elucidated using immunohistochemical staining.Results. qRT-PCR showed that the neuroligin-1 and neurexin II mRNA expressions of groups E16, E18, E20, and Ep0 increased gradually with the growth of embryonic rats (P<0.05). Western blotting confirmed the increasing tendency. In immunohistochemical staining, proteins neuroligin-1 and neurexin IIαpositive cells concentrated mostly in the myenteric nerve plexus of the colon and their expressions depend on the embryonic time.Conclusion. Neuroligin-1 and neurexin II were both expressed in the ENS and have temporal correlation with the development of ENS, during which neuronal intestinal malformations (NIM) may occur due to their disruptions and consequent abnormal ENS development.
Influence of Impurities on the Radiation Response of the TlBr Semiconductor Crystal
Authors: dos Santos Robinson Alves , de Mesquita Carlos Henrique , da Silva Júlio Batista Rodrigues , Ferraz Caue de Melo , da Costa Fabio Eduardo , Martins João Francisco Trencher , Gennari Roseli Fernandes , Hamada Margarida Mizue
Published: January 2017

Two commercially available TlBr salts were used as the raw material for crystal growths to be used as radiation detectors. Previously, TlBr salts were purified once, twice, and three times by the repeated Bridgman method. The purification efficiency was evaluated by inductively coupled plasma mass spectroscopy (ICP-MS), after each purification process. A compartmental model was proposed to fit the impurity concentration as a function of the repetition number of the Bridgman growths, as well as determine the segregation coefficients of impurities in the crystals. The crystalline structure, the stoichiometry, and the surface morphology of the crystals were evaluated, systematically, for the crystals grown with different purification numbers. To evaluate the crystal as a radiation semiconductor detector, measurements of its resistivity and gamma-ray spectroscopy were carried out, using 241Am and 133Ba sources. A significant improvement of the radiation response was observed in function of the crystal purity.
Relationships between Stress Granules, Oxidative Stress, and Neurodegenerative Diseases
Authors: Chen Lihua , Liu Beidong
Published: January 2017

Cytoplasmic stress granules (SGs) are critical for facilitating stress responses and for preventing the accumulation of misfolded proteins. SGs, however, have been linked to the pathogenesis of neurodegenerative diseases, in part because SGs share many components with neuronal granules. Oxidative stress is one of the conditions that induce SG formation. SGs regulate redox levels, and SG formation in turn is differently regulated by various types of oxidative stress. These associations and other evidences suggest that SG formation contributes to the development of neurodegenerative diseases. In this paper, we review the regulation of SG formation/assembly and discuss the interactions between oxidative stress and SG formation. We then discuss the links between SGs and neurodegenerative diseases and the current therapeutic approaches for neurodegenerative diseases that target SGs.
Robust Retinal Blood Vessel Segmentation Based on Reinforcement Local Descriptions
Authors: Li Meng , Ma Zhenshen , Liu Chao , Zhang Guang , Han Zhe
Published: January 2017

Retinal blood vessels segmentation plays an important role for retinal image analysis. In this paper, we propose robust retinal blood vessel segmentation method based on reinforcement local descriptions. A novel line set based feature is firstly developed to capture local shape information of vessels by employing the length prior of vessels, which is robust to intensity variety. After that, local intensity feature is calculated for each pixel, and then morphological gradient feature is extracted for enhancing the local edge of smaller vessel. At last, line set based feature, local intensity feature, and morphological gradient feature are combined to obtain the reinforcement local descriptions. Compared with existing local descriptions, proposed reinforcement local description contains more local information of local shape, intensity, and edge of vessels, which is more robust. After feature extraction, SVM is trained for blood vessel segmentation. In addition, we also develop a postprocessing method based on morphological reconstruction to connect some discontinuous vessels and further obtain more accurate segmentation result. Experimental results on two public databases (DRIVE and STARE) demonstrate that proposed reinforcement local descriptions outperform the state-of-the-art method.
Signal Factors Secreted by 2D and Spheroid Mesenchymal Stem Cells and by Cocultures of Mesenchymal Stem Cells Derived Microvesicles and Retinal Photoreceptor Neurons
Authors: Xie Lili , Mao Mao , Zhou Liang , Zhang Lusi , Jiang Bing
Published: January 2017

We aim to identify levels of signal factors secreted by MSCs cultured in 2D monolayers (2D-MSCs), spheroids (spheroids MSCs), and cocultures of microvesicles (MVs) derived from 2D-MSCs or spheroid MSCs and retinal photoreceptor neurons. We seeded 2D-MSCs, spheroid MSCs, and cells derived from spheroids MSCs at equal numbers. MVs isolated from all 3 culture conditions were incubated with 661W cells. Levels of 51 signal factors in conditioned medium from those cultured conditions were quantified with bead-based assay. We found that IL-8, IL-6, and GROαwere the top three most abundant signal factors. Moreover, compared to 2D-MSCs, levels of 11 cytokines and IL-2Rαwere significantly increased in conditioned medium from spheroid MSCs. Finally, to test if enhanced expression of these factors reflects altered immunomodulating activities, we assessed the effect of 2D-MSC-MVs and 3D-MSC-MVs on CD14+ cell chemoattraction. Compared to 2D-MSC-MVs, 3D-MSC-MVs significantly decreased the chemotactic index of CD14+ cells. Our results suggest that spheroid culture conditions improve the ability of MSCs to selectively secrete signal factors. Moreover, 3D-MSC-MVs also possessed an enhanced capability to promote signal factors secretion compared to 2D-MSC-MVs and may possess enhanced immunomodulating activities and might be a better regenerative therapy for retinal degenerative diseases.
An Analytical Model for the Identification of the Threshold of Stress Intensity Factor Range for Crack Growth
Authors: Grasso Marzio , De Iorio Antonio , Xu Yigeng , Haritos George , Mohin M. , Chen Yong K.
Published: January 2017

The value of the stress intensity factor (SIF) range thresholdΔKthfor fatigue crack growth (FCG) depends highly on its experimental identification. The identification and application ofΔKthare not well established as its determination depends on various factors including experimental, numerical, or analytical techniques used. A new analytical model which can fit the raw FCG experimental data is proposed. The analytical model proposed is suitable to fit with high accuracy the experimental data and is capable of estimating the threshold SIF range. The comparison between the threshold SIF range identified with the model proposed and those found in the literature is also discussed.ΔKthidentified is found to be quite accurate and consistent when compared to the literature with a maximum deviation of 5.61%. The accuracy with which the analytical model is able to fit the raw data is also briefly discussed.
Ventricular Tachycardia Originating from Moderator Band: New Perspective on Catheter Ablation
Authors: Li Jin-yi , Jiang Jing-bo , He Yan , Luo Jian-chun , Zhong Guo-qiang
Published: January 2017

A 59-year-old woman was referred to the institution with burdens of idiopathic ventricular tachycardia (IVT). Electroanatomic mapping revealed a complex fractionated, high frequency potential with long duration preceding the QRS onset of the IVT. The real end point of ablation was the disappearance of the conduction block of Purkinje potential during the sinus rhythm besides the disappearance of the inducible tachycardia. Location of distal catheter was at the moderator band (MB) by transthoracic echocardiography (TTE). Only irrigated radiofrequency current was delivered at both insertions of the MB which can completely eliminate the IVT.
Bond-Slip Models for FPR-Concrete Interfaces Subjected to Moisture Conditions
Authors: Shrestha Justin , Zhang Dawei , Ueda Tamon
Published: January 2017

Environmental related durability issues have been of great concerns in the structures strengthened with the fiber reinforced polymers (FRPs). In marine environment, moisture is one of the dominant factors that adversely affect the material properties and the bond interfaces. Several short-term and long-term laboratory experimental investigations have been conducted to study such behaviors but, still, there are insufficient constitutive bond models which could incorporate moisture exposure conditions. This paper proposed a very simple approach in determining the nonlinear bond-slip models for the FRP-concrete interface considering the effect of moisture conditions. The proposed models are based on the strain results of the experimental investigation conducted by the authors using 6 different commercial FRP systems exposed to the moisture conditions for the maximum period of 18 months. The exposure effect in the moisture conditions seems to have great dependency on the FRP system. Based on the contrasting differences in the results under moisture conditions, separate bond-slip models have been proposed for the wet-layup FRP and prefabricated FRP systems. As for the verification of the proposed model under moisture conditions, predicted pull-out load was compared with the experimental pull-out load. The results showed good agreement for all the FRP systems under investigation.
Vision Loss and Recovery after Baerveldt Aqueous Tube Shunt Implantation
Authors: Kim Esther Lee , Tran Jeffrey , Töteberg-Harms Marc , Chahal Jasdeep , Rhee Douglas , Chopra Vikas , Francis Brian
Published: January 2017

This study aims to determine the course of vision loss after Baerveldt aqueous tube shunt placement and identify risk factors associated with unexplained severe long-term vision loss, or snuff-out. We retrospectively reviewed 247 eyes of 222 patients who underwent Baerveldt implantations at one of two academic institutions. Postoperative vision loss at 6 months following surgery was categorized as mild-to-moderate versus severe and long-term versus transient. Long-term vision loss, defined as 3 or more lines of Snellen visual acuity (VA) loss compared with preoperative VA, occurred in 63 of 247 eyes (25.5%), and 39 had mild-to-moderate and 24 had severe loss. Of these 63 eyes, 18 had no identifiable cause of vision loss. On multivariate analysis, poorer Snellen VA on postoperative day 1 (POD1) was found to be a significant risk factor for long-term vision loss (p=0.005). In addition, the negative change in preoperative versus POD1 Snellen VA (p=0.021) and the presence of split fixation involving the inferonasal quadrant on preoperative Humphrey visual field (p=0.044) were significant risk factors for snuff-out. Transient vision loss occurred in 76 of 242 eyes (30.8%). In conclusion, vision loss is not uncommon after Baerveldt surgery, with snuff-out occurring in 2.4% of cases in this study.
Effect of R119G Mutation on Human P5CR1 Dynamic Property and Enzymatic Activity
Authors: Li Linhua , Ye Yujia , Sang Peng , Yin Yirui , Hu Wei , Wang Jing , Zhang Chao , Li Deyun , Wan Wen , Li Rui , Li Longjun , Ma Linling , Xie Yuehui , Meng Zhaohui
Published: January 2017

Pyrroline-5-carboxylate reductase (P5CR1) is a universal housekeeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline with concomitant oxidation of NAD(P)H to NAD(P)+. The enzymatic cycle between P5C and proline is important for function in amino acid metabolism, apoptosis, and intracellular redox potential balance in mitochondria. Autosomal recessive cutis laxa (ARCL) results from a mutation in P5CR1 encoded by PYCR1. Specifically, the R119G mutation is reported to be linked to ARCL although it has not yet been characterized. We synthesized R119G P5CR1 and compared it to WT P5CR1. Foldx prediction of WT and R119G mutant P5CR1 protein stability suggests that the R119G mutation could significantly reduce protein stability. We also performed enzymatic activity assays to determine how the mutation impacts P5CR1 enzymatic function. The results of these experiments show that mutagenesis of R119 to G decreases P5CR1 catalytic efficiency for 3,4-dehydro-L-proline relative to WT. Mutagenesis and kinetic studies reveal that the activity of the mutant decreases as temperature increases from 5°C to 37°C, with almost no activity at 37°C, indicating that this mutation impairs P5CR1 function in vivo. Conversely, WT P5CR1 retains its activity after incubation at 37°C and has essentially no remaining activity at 75°C. Taken together, our experimental results indicate the R119G mutation could be an involving pathomechanism for ARCL.
Neuromuscular Coordination Deficit Persists 12 Months after ACL Reconstruction But Can Be Modulated by 6 Weeks of Kettlebell Training: A Case Study in Women’s Elite Soccer
Authors: Zebis Mette K. , Andersen Christoffer H. , Bencke Jesper , Ørntoft Christina , Linnebjerg Connie , Hölmich Per , Thorborg Kristian , Aagaard Per , Andersen Lars L.
Published: January 2017

The aim of the present single-case study was to investigate the effect of 6 weeks’ kettlebell training on the neuromuscular risk profile for ACL injury in a high-risk athlete returning to sport after ACL reconstruction. A female elite soccer player (age 21 years) with no previous history of ACL injury went through neuromuscular screening as measured by EMG preactivity of vastus lateralis and semitendinosus during a standardized sidecutting maneuver. Subsequently, the player experienced a noncontact ACL injury. The player was screened again following postreconstruction rehabilitation, then underwent 6-week kettlebell training, and was subsequently screened again at 6-week follow-up. Prior to and after postreconstruction rehabilitation the player demonstrated a neuromuscular profile during sidecutting known to increase the risk for noncontact ACL injury, that is, reduced EMG preactivity for semitendinosus and elevated EMG preactivity for vastus lateralis. Subsequently, the 6-week kettlebell training increased semitendinosus muscle preactivity during sidecutting by 38 percentage points to a level equivalent to a neuromuscular low-risk profile. An ACL rehabilitated female athlete with a high-risk neuromuscular profile changed to low-risk in response to 6 weeks of kettlebell training. Thus, short-term kettlebell exercise with documented high levels of medial hamstring activation was found to transfer into high medial hamstring preactivation during a sidecutting maneuver.
Microstructure and Magnetic Properties of NdFeB Films through Nd Surface Diffusion Process
Authors: Liu Wenfeng , Zhang Mingang , Zhang Kewei , Chai Yuesheng
Published: January 2017

Ta/Nd/NdFeB/Nd/Ta films were deposited by magnetron sputtering on Si (100) substrates and subsequently annealed for 30 min at 923 K in vacuum. It was found that the microstructure and magnetic properties of Ta/Nd/NdFeB/Nd/Ta films strongly depend on the NdFeB layer thickness. With NdFeB layer thickness increasing, both the grain size and the strain firstly reduce and then increase. When NdFeB layer thickness is 750 nm, the strain reaches the minimum value. Meanwhile, both the in-plane and perpendicular coercivities firstly drastically increase and then slowly decrease with NdFeB layer thickness increasing. The highest in-plane and perpendicular coercivities can be obtained at NdFeB layer thickness of 750 nm, which are 21.2 kOe and 19.5 kOe, respectively. In addition, the high remanence ratio (remanent magnetization/saturation magnetization) of 0.87 can also be achieved in Ta/Nd/NdFeB (750 nm)/Nd/Ta film.
Diffusion Kurtosis Imaging Detects Microstructural Changes in the Brain after Acute Alcohol Intoxication in Rats
Authors: Chen Xi-ran , Zeng Jie-ying , Shen Zhi-Wei , Kong Ling-mei , Zheng Wen-bin
Published: January 2017

The aim of this study was to test the technical feasibility of diffusion kurtosis imaging (DKI) in the brain after acute alcohol intoxication. Diffusion tensor imaging (DTI) and DKI during 7.0 T MRI were performed in the frontal lobe and thalamus before and 30 min, 2 h, and 6 h after ethyl alcohol administration. Compared with controls, mean kurtosis values of the frontal lobe and thalamus first decreased by 44% and 38% within 30 min (p<0.01 all) and then increased by 14% and 46% at 2 h (frontal lobe, p>0.05; thalamus, p<0.01) and by 29% and 68% at 6 h (frontal lobe, p<0.05; thalamus, p<0.01) after acute intake. Mean diffusivity decreased significantly in both the frontal lobe and the thalamus at various stages. However, fractional anisotropy decreased only in the frontal lobe, with no detectable change in the thalamus. This demonstrates that DKI possesses sufficient sensitivity for tracking pathophysiological changes at various stages associated with acute alcohol intoxication and may provide additional information that may be missed by conventional DTI parameters.
Sliding Mode Control with PD Sliding Surface for High-Speed Railway Pantograph-Catenary Contact Force under Strong Stochastic Wind Field
Authors: Song Yang , Liu Zhigang , Ouyang Huajiang , Wang Hongrui , Lu Xiaobing
Published: January 2017

As is well known, the external disturbance (especially the stochastic wind load) has nonnegligible effect on the operation of pantograph-catenary system, which may cause the strong fluctuation in contact force as well as the increased occurrence of contact loss. In order to improve the current collection quality of a high-speed railway pantograph-catenary system under a strong stochastic wind field, a sliding mode controller with a proportional-derivative (PD) sliding surface for a high-speed active pantograph is proposed. The nonlinear finite element procedure is employed to establish the catenary model. The fluctuating wind speeds along catenary are simulated using empirical spectrums. The buffeting forces exerted on contact and messenger wires are derived to construct the stochastic wind field along the catenary. A PD sliding surface is properly determined to guarantee that the mechanical impedance of pantograph head at the dominant frequencies of contact force decreases when the sliding surface approaches zero. Through several numerical simulations with different wind velocities and wind angles, the control performance of two popular control laws (proportional switching law and constant switching law) is evaluated.
Symmetries and Properties of the Energy-Casimir Mapping in the Ball-Plate Problem
Authors: Lăzureanu Cristian , Bînzar Tudor
Published: January 2017

In this paper a system derived by an optimal control problem for the ball-plate dynamics is considered. Symplectic and Lagrangian realizations are given and some symmetries are studied. The image of the energy-Casimir mapping is described and some connections with the dynamics of the considered system are presented.
Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events
Authors: Okolo Onyemaechi N. , Katsanis Emmanuel , Yun Seongseok , Reveles Candace Y. , Anwer Faiz
Published: January 2017

Objective and Importance.Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk of infection.Case.A 25-year-old male diagnosed with CyN, on G-CSF but worsening quality of life. Pretransplant investigations revealed ELANE mutation positive severe CyN along with familial Mediterranean fever (MEFV) mutation.Intervention.Bone marrow transplantation as treatment for dual mutation (ELANE and MEFV mutation) positive severe CyN.Conclusion.BMT may be considered as an alternative treatment for severe CyN in patients who are refractory to G-CSF. It is postulated that in our patient the combined mutations (CyN and MEFV) may have contributed to the severity of this individual’s symptoms. We suggest CyN patients who present with severe symptoms have evaluation with ELANE mutation testing, Periodic Fever Syndromes Panel, and routine marrow assessment with FISH, conventional cytogenetics, and morphological evaluation for MDS/AML.
From Bad to Worse: Paraganglioma Diagnosis during Induction of Labor for Coexisting Preeclampsia
Authors: Dusitkasem Sasima , Herndon Blair H. , Paluzzi Dalton , Kuhn Joseph , Small Robert H. , Coffman John C.
Published: January 2017

Pheochromocytomas and extra-adrenal paragangliomas are catecholamine-secreting tumors that rarely occur in pregnancy. The diagnosis of these tumors in pregnancy can be challenging given that many of the signs and symptoms are commonly attributed to preeclampsia or other more common diagnoses. Early diagnosis and appropriate management are essential in optimizing maternal and fetal outcomes. We report a rare case of a catecholamine-secreting tumor in which diagnosis occurring at the time labor was being induced for concomitant preeclampsia with severe features. Her initial presentation in hypertensive crisis with other symptoms led to diagnostic workup for secondary causes of hypertension and led to eventual diagnosis of paraganglioma. Obtaining this diagnosis prior to delivery was essential, as this led to prompt multidisciplinary care, changed the course of her clinical management, and ultimately enabled good maternal and fetal outcomes. This case highlights the importance of maintaining a high index of suspicion for secondary causes of hypertension and in obstetric patients and providing timely multidisciplinary care.
Maize Fungal Growth Control with Scopoletin of Cassava Roots Produced in Benin
Authors: Ba Rafiatou , Alfa Teou , Gbaguidi Fernand , Novidzro Kosi Mawuéna , Dotse Kokouvi , Koudouvo Koffi , Houngue Ursula , Donou Hounsode Marcel T. , Koumaglo Kossi Honoré , Ameyapoh Yaovi , Baba-Moussa Lamine
Published: January 2017

The chemical contamination of food is among the main public health issues in developing countries. With a view to find new natural bioactive products against fungi responsible for chemical contamination of staple food such as maize, the antifungal activity tests of scopoletin extracted from different components of the cassava root produced in Benin were carried out. The dosage of scopoletin from parts of the root (first skin, second skin, whole root, and flesh) was done by High Performance Liquid Chromatography. The scopoletin extract was used to assess the activity of 12 strains (11 strains of maize and a reference strain). The presence of scopoletin was revealed in all components of the cassava root. Scopoletin extracted from the first skin cassava root was the most active both as inhibition of sporulation (52.29 to 87.91%) and the mycelial growth (36.51–80.41%). Scopoletin extract from the cassava root skins showed significant inhibitory activity on the tested strains with fungicide concentration (MFC) between 0.0125 mg/mL and 0.1 mg/mL. The antifungal scopoletin extracted from the cassava root skins may be well beneficial for the fungal control of the storage of maize.
Andrographolide Inhibits Proliferation and Metastasis of SGC7901 Gastric Cancer Cells
Authors: Dai Lei , Wang Gang , Pan Wensheng
Published: January 2017

To explore the mechanisms by which andrographolide inhibits gastric cancer cell proliferation and metastasis, we employed the gastric cell line SGC7901 to investigate the anticancer effects of andrographolide. The cell survival ratio, cell migration and invasion, cell cycle, apoptosis, and matrix metalloproteinase activity were assessed. Moreover, western blotting and real-time PCR were used to examine the protein expression levels and the mRNA expression levels, respectively. The survival ratio of cells decreased with an increasing concentration of andrographolide in a dose-dependent manner. Consistent results were also obtained using an apoptosis assay, as detected by flow cytometry. The cell cycle was blocked at the G2/M2 phase by andrographolide treatment, and the proportion of cells arrested at G1/M was enhanced as the dose increased. Similarly, wound healing and Transwell assays showed reduced migration and invasion of the gastric cancer cells at various concentrations of andrographolide. Andrographolide can inhibit cell proliferation, invasion, and migration, block the cell cycle, and promote apoptosis in SGC7901 cells. The mechanisms may include upregulated expression of Timp-1/2, cyclin B1, p-Cdc2, Bax, and Bik and downregulated expression of MMP-2/9 and antiapoptosis protein Bcl-2.
An Automated Structural Optimisation Methodology for Scissor Structures Using a Genetic Algorithm
Authors: Koumar Aushim , Tysmans Tine , Filomeno Coelho Rajan , De Temmerman Niels
Published: January 2017

We developed a fully automated multiobjective optimisation framework using genetic algorithms to generate a range of optimal barrel vault scissor structures. Compared to other optimisation methods, genetic algorithms are more robust and efficient when dealing with multiobjective optimisation problems and provide a better view of the search space while reducing the chance to be stuck in a local minimum. The novelty of this work is the application and validation (using metrics) of genetic algorithms for the shape and size optimisation of scissor structures, which has not been done so far for two objectives. We tested the feasibility and capacity of the methodology by optimising a 6 m span barrel vault to weight and compactness and by obtaining optimal solutions in an efficient way using NSGA-II. This paper presents the framework and the results of the case study. The in-depth analysis of the influence of the optimisation variables on the results yields new insights which can help in making choices with regard to the design variables, the constraints, and the number of individuals and generations in order to obtain efficiently a trade-off of optimal solutions.
DisseminatedMycobacterium interjectumInfection with Bacteremia, Hepatic and Pulmonary Involvement Associated with a Long-Term Catheter Infection
Authors: Sotello David , Hata D. Jane , Reza Mohammed , Satyanarayana Raj , Arunthari Vichaya , Bosch Wendelyn
Published: January 2017

We present a 49-year-old female with one year of intermittent fevers, chills, night sweats, and significant weight loss. Liver and lung biopsy showed evidence of a granulomatous process. Blood and liver biopsy cultures yielded growth of presumedMycobacterium interjectum, thought to be related to a disseminated long-term central venous catheter infection. She successfully received one year of combined antimicrobial therapy after catheter removal without recurrence of disease.M. interjectumhas been previously described as a cause of lymphadenitis in healthy children and associated with pulmonary disease in adults, although other localized infections have been reported. This is the first case described of a disseminatedM. interjectuminfection with bacteremia, hepatic and pulmonary involvement associated with a long-term catheter infection.
Acute “Pseudoischemic” ECG Abnormalities after Right Pneumonectomy
Authors: Vasic Nada , Dimic-Janjic Sanja , Stevic Ruza , Milenkovic Branislava , Djukanovic Verica
Published: January 2017

New onset of electrocardiographic (ECG) abnormalities can occur after lung surgery due to the changes in the position of structures and organs in the chest cavity. The most common heart rhythm disorder is atrial fibrillation. So-called “pseudoischemic” ECG changes that mimic classic ECG signs of acute myocardial ischemia are also often noticed. We report the case of a 68-year-old male, with no prior cardiovascular disease, who underwent extensive surgical resection for lung cancer. On a second postoperative day, clinical and electrocardiographic signs of acute myocardial ischemia occurred. According to clinical course, diagnostic procedures, and therapeutic response, we excluded acute coronary syndrome. We concluded that physical lesion of the pericardium, caused by extended pneumonectomy with resection of the pericardium, provoked the symptoms and ECG signs that mimic acute coronary syndrome. Our final diagnosis was postpericardiotomy syndrome after extended pneumonectomy and further treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) was recommended. It is necessary to consider possibility that nature of ECG changes after extended pneumonectomy could be “pseudoischemic.”
Pharmacokinetic Properties of Adenosine Amine Congener in Cochlear Perilymph after Systemic Administration
Authors: Chang Hao , Telang Ravindra S. , Sreebhavan Sreevalsan , Tingle Malcolm , Thorne Peter R. , Vlajkovic Srdjan M.
Published: January 2017

Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown previously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors in the inner ear, and a selective A1adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially effective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties of ADAC in rat perilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry detection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy, precision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with the cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and remained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC was significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or cochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural hearing loss caused by exposure to traumatic noise.
Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging
Authors: Müller Andreas , Hochrath Katrin , Stroeder Jonas , Hittatiya Kanishka , Schneider Günther , Lammert Frank , Buecker Arno , Fries Peter
Published: January 2017

Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 andT2⁎may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 andT2⁎in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination ofT2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout(Abcb4 -/-)mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 andT2⁎correlate differently to disease severity and etiology of liver fibrosis.T2⁎shows significant decrease correlating with fibrosis in CCl4treated animals, while demonstrating significant increase with disease severity inAbcb4 -/-mice. Measurements of T1 andT2⁎may therefore facilitate discrimination between different stages and causes of liver fibrosis.
Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)
Authors: Masuda Tomomi , Shimazawa Masamitsu , Hara Hideaki
Published: January 2017

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age‐related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.
Hodgkin Lymphoma and Castleman Disease: When One Blood Disease Can Hide Another
Authors: Filliatre-Clement L. , Busby-Venner H. , Moulin C. , Roth-Guepin G. , Perrot A.
Published: January 2017

We describe a rare case of Castleman disease associated de novo with Hodgkin lymphoma. The incidence of Castleman disease is rare; only a few studies have described it in de novo association with Hodgkin lymphoma. The patient described here complained of unique evolutionary axillary adenopathy. A positron-emission tomography/computed tomography scan revealed hypermetabolic activity in this area. Diagnosis was based on a total excision biopsy of the adenopathy. The patient underwent complete remission with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy for treating Hodgkin lymphoma after surgical excision of the unicentric Castleman disease lesion.
A Mixed Methods Small Pilot Study to Describe the Effects of Upper Limb Training Using a Virtual Reality Gaming System in People with Chronic Stroke
Authors: Stockley Rachel C. , O’Connor Deborah A. , Smith Phil , Moss Sylvia , Allsop Lizzie , Edge Wendy
Published: January 2017

Introduction. This small pilot study aimed to examine the feasibility of an upper limb rehabilitation system (the YouGrabber) in a community rehabilitation centre, qualitatively explore participant experiences, and describe changes after using it. Methods and Material. Chronic stroke participants attending a community rehabilitation centre in the UK were randomised to either a YouGrabber or a gym group and completed 18 training sessions over 12 weeks. The motor activity log, box and block, and fatigue severity score were administered by a blinded assessor before and after the intervention. Semistructured interviews were used to ascertain participants’ views about using the YouGrabber. Results. Twelve participants (6 females) with chronic stroke were recruited. All adhered to the intervention. There were no adverse events, dropouts, or withdrawal. There were no significant differences between the YouGrabber and gym groups although there were significant within group improvements on the motor activity log (median change: 0.59, range: 0.2–1.25; p<0.05) within the YouGrabber group. Participants reported that the YouGrabber was motivational but they expressed frustration with technical challenges. Conclusions. The YouGrabber appeared practical and may improve upper limb activities in people several months after stroke. Future work could examine cognition, cost effectiveness, and different training intensities.
Anti-Folate Receptor-α IgE but not IgG Recruits Macrophages to Attack Tumors via TNFα/MCP-1 Signaling
Authors: Josephs Debra H. , Bax Heather J. , Dodev Tihomir , Georgouli Mirella , Nakamura Mano , Pellizzari Giulia , Saul Louise , Karagiannis Panagiotis , Cheung Anthony , Herraiz Cecilia , Ilieva Kristina M. , Correa Isabel , Fittall Matthew , Crescioli Silvia , Gazinska Patrycja , Woodman Natalie , Mele Silvia , Chiaruttini Giulia , Gilbert Amy E. , Koers Alexander , Bracher Marguerite , Selkirk Christopher , Lentfer Heike , Barton Claire , Lever Elliott , Muirhead Gareth , Tsoka Sophia , Canevari Silvana , Figini Mariangela , Montes Ana , Downes Noel , Dombrowicz David , Corrigan Christopher J. , Beavil Andrew J. , Nestle Frank O. , Jones Paul S. , Gould Hannah J. , Sanz-Moreno Victoria , Blower Philip J. , Spicer James F. , Karagiannis Sophia N.
Published: January 2017

IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibody-dependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen–specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms were undefined and in vivo proof of concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fcϵ receptor system for cancer studies. We also generated rat IgE and IgG mAbs specific for the folate receptor (FRα), which is expressed widely on human ovarian tumors, along with a syngeneic rat tumor model expressing human FRα. Compared with IgG, anti-FRα IgE reduced lung metastases. This effect was associated with increased intratumoral infiltration by TNFα+ and CD80+ macrophages plus elevated TNFα and the macrophage chemoattractant MCP-1 in lung bronchoalveolar lavage fluid. Increased levels of TNFα and MCP-1 correlated with IgE-mediated tumor cytotoxicity by human monocytes and with longer patient survival in clinical specimens of ovarian cancer. Monocytes responded to IgE but not IgG exposure by upregulating TNFα, which in turn induced MCP-1 production by monocytes and tumor cells to promote a monocyte chemotactic response. Conversely, blocking TNFα receptor signaling abrogated induction of MCP-1, implicating it in the antitumor effects of IgE. Overall, these findings show how antitumor IgE reprograms monocytes and macrophages in the tumor microenvironment, encouraging the clinical use of IgE antibody technology to attack cancer beyond the present exclusive reliance on IgG. Cancer Res; 77(5); 1127–41. ©2017 AACR.