bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the tryptophan residues in proton-coupled folate transporter (PCFT-SLC46A1) function
Authors: Najmi Mitra , Zhao Rongbao , Fiser Andras , Goldman I. David
Published: June 2016

The proton-coupled folate transporter (PCFT) mediates folate absorption across the brush-border membrane of the proximal small intestine and is required for folate transport across the choroid plexus into the cerebrospinal fluid. In this study, the functional role and accessibility of the seven PCFT Trp residues were assessed by the substituted-cysteine accessibility method. Six Trp residues at a lipid-aqueous interface tolerated Cys substitution in terms of protein stability and function. W85C, W202C, and W213C were accessible to N-biotinyl aminoethylmethanethiosulfonate; W48C and W299C were accessible only after treatment with dithiotreitol (DTT), consistent with modification of these residues by an endogenous thiol-reacting molecule and their extracellular location. Neither W107C nor W333C was accessible (even after DTT) consistent with their cytoplasmic orientation. Biotinylation was blocked by pemetrexed only for the W48C (after DTT), W85C, W202C residues. Function was impaired only for the W299C PCFT mutant located in the 4th external loop between the 7th and 8th transmembrane helices. Despite its aqueous location, function could only be fully preserved with Phe and, to a lesser extent, Ala substitutions. There was a 6.5-fold decrease in the pemetrexed influx Vmax and a 3.5- and 6-fold decrease in the influx Kt and Ki, respectively, for the W299S PCFT. The data indicate that the hydrophobicity of the W299 residue is important for function suggesting that during the transport cycle this residue interacts with the lipid membrane thereby impacting on the oscillation of the carrier and, indirectly, on the folate binding pocket.
Myo-inositol phosphate synthase expression in the European eel (Anguilla anguilla) and Nile tilapia (Oreochromis niloticus): effect of seawater acclimation
Authors: Kalujnaia Svetlana , Hazon Neil , Cramb Gordon
Published: June 2016

A single MIPS gene ( Isyna1/ Ino1) exists in eel and tilapia genomes with a single myo-d-inositol 3-phosphate synthase (MIPS) transcript identified in all eel tissues, although two MIPS spliced variants [termed MIPS(s)and MIPS(l)] are found in all tilapia tissues. The larger tilapia transcript [MIPS(l)] results from the inclusion of the 87-nucleotide intron between exons 5 and 6 in the genomic sequence. In most tilapia tissues, the MIPS(s)transcript exhibits much higher abundance (generally >10-fold) with the exception of white skeletal muscle and oocytes, in which the MIPS(l)transcript predominates. SW acclimation resulted in large (6- to 32-fold) increases in mRNA expression for both MIPS(s)and MIPS(l)in all tilapia tissues tested, whereas in the eel, changes in expression were limited to a more modest 2.5-fold increase and only in the kidney. Western blots identified a number of species- and tissue-specific immunoreactive MIPS proteins ranging from 40 to 67 kDa molecular weight. SW acclimation failed to affect the abundance of any immunoreactive protein in any tissue tested from the eel. However, a major 67-kDa immunoreactive protein (presumed to be MIPS) found in tilapia tissues exhibited 11- and 54-fold increases in expression in gill and fin samples from SW-acclimated fish. Immunohistochemical investigations revealed specific immunoreactivity in the gill, fin, skin, and intestine taken from only SW-acclimated tilapia. Immunofluorescence indicated that MIPS was expressed within gill chondrocytes and epithelial cells of the primary filaments, basal epithelial cell layers of the skin and fin, the cytosol of columnar intestinal epithelial and mucous cells, as well as unknown entero-endocrine-like cells.
Sexually dimorphic myeloid inflammatory and metabolic responses to diet-induced obesity
Authors: Griffin C. , Lanzetta N. , Eter L. , Singer K.
Published: June 2016

It is well known in clinical and animal studies that women and men have different disease risk as well as different disease physiology. Women of reproductive age are protected from metabolic and cardiovascular disease compared with postmenopausal women and men. Most murine studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of similar protection in female mice. We have investigated dietary obesity in a mouse model and have directly compared inflammatory responses in males and females. In this review we will summarize what is known about sex differences in diet-induced inflammation and will summarize our data on this topic. It is clear that sex differences in high-fat diet-induced inflammatory activation are due to cell intrinsic differences in hematopoietic responses to obesogenic cues, but further research is needed to understand what leads to sexually dimorphic responses.
Late intervention with the small molecule BB3 mitigates postischemic kidney injury
Authors: Narayan Prakash , Duan Bin , Jiang Kai , Li Jingsong , Paka Latha , Yamin Michael A. , Friedman Scott L. , Weir Matthew R. , Goldberg Itzhak D.
Published: June 2016

Ischemia-reperfusion-mediated acute kidney injury can necessitate renal replacement therapy and is a major cause of morbidity and mortality. We have identified BB3, a small molecule, which when first administered at 24 h after renal ischemia in rats, improved survival, augmented urine output, and reduced the increase in serum creatinine and blood urea nitrogen. Compared with control kidneys, the kidneys of BB3-treated animals exhibited reduced levels of kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and reduced tubular apoptosis and acute tubular necrosis but enhanced tubular regeneration. Consistent with its hepatocyte growth factor-like mode of action, BB3 treatment promoted phosphorylation of renal cMet and Akt and upregulated renal expression of the survival protein Bcl-2. These data suggest that the kidney is amenable to pharmacotherapy even 24 h after ischemia-reperfusion and that activation of the hepatocyte growth factor signaling pathway with the small molecule BB3 confers interventional benefits late into ischemia-reperfusion injury. These data formed, in part, the basis for the use of BB3 in a clinical trial in kidney recipients presenting with delayed graft function.
Beyond cones: an improved model of whisker bending based on measured mechanics and tapering
Authors: Hires Samuel Andrew , Schuyler Adam , Sy Jonathan , Huang Vincent , Wyche Isis , Wang Xiyue , Golomb David
Published: June 2016

The sense of touch is represented by neural activity patterns evoked by mechanosensory input forces. The rodent whisker system is exceptional for studying the neurophysiology of touch in part because these forces can be precisely computed from video of whisker deformation. We evaluate the accuracy of a standard model of whisker bending, which assumes quasi-static dynamics and a linearly tapered conical profile, using controlled whisker deflections. We find significant discrepancies between model and experiment: real whiskers bend more than predicted upon contact at locations in the middle of the whisker and less at distal locations. Thus whiskers behave as if their stiffness near the base and near the tip is larger than expected for a homogeneous cone. We assess whether contact direction, friction, inhomogeneous elasticity, whisker orientation, or nonconical shape could explain these deviations. We show that a thin-middle taper of mouse whisker shape accounts for the majority of this behavior. This taper is conserved across rows and columns of the whisker array. The taper has a large effect on the touch-evoked forces and the ease with which whiskers slip past objects, which are key drivers of neural activity in tactile object localization and identification. This holds for orientations with intrinsic whisker curvature pointed toward, away from, or down from objects, validating two-dimensional models of simple whisker-object interactions. The precision of computational models relating sensory input forces to neural activity patterns can be quantitatively enhanced by taking thin-middle taper into account with a simple corrective function that we provide.
Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance
Authors: Saad M. J. A. , Santos A. , Prada P. O.
Published: June 2016

Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities.
Aromatase: Contributions to Physiology and Disease in Women and Men
Authors: Blakemore Jennifer , Naftolin Fredrick
Published: June 2016

Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products.
New Method of Parent Catheter Advancement in the Balloon Anchor Technique during Balloon-Occluded Transarterial Chemoembolization for Hepatic Tumors
Authors: Shibuya Kei , Tahara Hiroki , Takeuchi Suguru , Koyama Yoshinori , Tsushima Yoshito
Published: May 2016

Balloon-occluded transarterial chemoembolization (B-TACE) using a microballoon catheter is a promising method for improvement of lipiodol emulsion accumulation and local control relative to conventional transarterial chemoembolization. This method has been referred to as the balloon anchor technique in previous reports. We report a new technique for successful parent catheter advancement for achievement of stable backup for the selective insertion of a microballoon catheter during B-TACE using the microballoon as an anchor, even in patients with tortuous anatomy of the hepatic and celiac arteries. Deep cannulation of parent catheters was accomplished in all three cases and complications such as vascular injury were not observed in the postprocedure angiograms.
Missile-Borne SAR Raw Signal Simulation for Maneuvering Target
Authors: Xia Weijie , Qi Yuanyuan , Huang Linlin , Jin Xue
Published: June 2016

SAR raw signal simulation under the case of maneuver and high-speed has been a challenging and urgent work recently. In this paper, a new method based on one-dimensional fast Fourier transform (1DFFT) algorithm is presented for raw signal simulation of maneuvering target for missile-borne SAR. Firstly, SAR time-domain raw signal model is given and an effective Range Frequency Azimuth Time (RFAT) algorithm based on 1DFFT is derived. In this algorithm, the “Stop and Go” (SaG) model is adopted and the wide radar scattering characteristic of target is taken into account. Furthermore, the “Inner Pulse Motion” (IPM) model is employed to deal with high-speed case. This new RFAT method can handle the maneuvering cases, high-speed cases, and bistatic radar cases, which are all possible in the missile-borne SAR. Besides, this raw signal simulation adopts the electromagnetic scattering calculation so that we do not need a scattering rate distribution map as the simulation input. Thus, the multiple electromagnetic reflections can be considered. Simulation examples prove the effectiveness of our method.
A Novel Fuzzy Level Set Approach for Image Contour Detection
Authors: Zhang Yingjie , Xu Jianxing , Cheng H. D.
Published: June 2016

The level set methods have provided powerful frameworks for image segmentation. However, to obtain accurate boundaries of the objects, especially when they have weak edges or inhomogeneous intensities, is still a very challenging task. Actually, we have studied the popular existing level set approaches and discovered that they failed to segment the images with weak edges or inhomogeneous intensities in many cases. The weak/blurry edges and inhomogeneous intensities cause uncertainty and fuzziness for segmentation. In this paper, a novel fuzzy level set approach is proposed. At first,S-function based on the maximum fuzzy entropy principle (MEP) is used to map the image from space domain to fuzzy domain. Then, an energy function is formulated according to the differences between the actual and estimated probability densities of the intensities in different regions. A partial differential equation is derived for finding the minimum of the energy function. The proposed approach has been tested on both synthetic images and real images and evaluated by several popular metrics. The experimental results demonstrate that the proposed approach can locate the true object boundaries, even for objects with blurry boundaries, low contrast, and inhomogeneous intensities.
Intra- and Extracranial MR Venography: Technical Notes, Clinical Application, and Imaging Development
Authors: Paoletti M. , Germani G. , De Icco R. , Asteggiano C. , Zamboni P. , Bastianello S.
Published: May 2016

Scientific debate over chronic cerebrospinal venous insufficiency (CCSVI) has drawn attention to venous system involvement in a series of pathologic brain conditions. In the last few decades, the MRI venography (MRV) field has developed a number of valuable sequences to better investigate structural anatomy, vessel patency, and flow characteristics of venous drainage in the intra- and extracranial systems. A brief two-tier protocol is proposed to encompass the study of intra- and extracranial venous drainage with and without contrast administration, respectively. Contrast-enhanced protocol is based on time-resolved contrast-enhanced MRV of the whole region plus extracranial flow quantification through 2D Cine phase contrast (PC); non-contrast-enhanced protocol includes intracranial 3D PC, extracranial 2D time of flight (TOF), and 2D Cine PC flow quantification. Total scanning time is reasonable for clinical applications: approximately seven minutes is allocated for the contrast protocol (most of which is due to 2D Cine PC), while the noncontrast protocol accounts for around twenty minutes. We believe that a short though exhaustive MRI scan of the whole intra- and extracranial venous drainage system can be valuable for a variety of pathologic conditions, given the possible venous implication in several neurological conditions.
Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke
Authors: Farhana Kun Marisa , Malueka Rusdy Ghazali , Wibowo Samekto , Gofir Abdul
Published: June 2016

This study aimed to determine the effectiveness of gotu kola (Centella asiatica) in improving cognitive function in patients with vascular cognitive impairment (VCI). This study uses a quasi‐experimental design. Subjects in this study were patients with poststroke cognitive impairment who were treated at two hospitals in Yogyakarta, Indonesia. The number of subjects was 48: 17 subjects were treated with 1000 mg/day of gotu kola extract, 17 subjects treated with 750 mg/day of gotu kola extract, and 14 subjects treated with 3 mg/day of folic acid for 6 weeks. A Montreal Cognitive Assessment‐Indonesian version (MoCA‐Ina) was conducted at the beginning of treatment and after 6 weeks of therapy. It was found that all trials effectively improved poststroke VCI based on MoCA‐Ina scores over the course of the study. There is no significant difference in ΔMoCA‐Ina (score at the 6th week of treatment − score at the beginning) mean score among the three groups, indicating that gotu kola is as effective as folic acid in improving poststroke VCI. Gotu kola was shown to be more effective than folic acid in improving memory domain. This study suggested that gotu kola extract is effective in improving cognitive function after stroke.
Rigid Body Inertia Estimation Using Extended Kalman and Savitzky-Golay Filters
Authors: Kim Donghoon , Yang Sungwook , Lee Sangchul
Published: June 2016

Inertia properties of rigid body such as ground, aerial, and space vehicles may be changed by several occasions, and this variation of the properties influences the control accuracy of the rigid body. For this reason, accurate inertia properties need to be obtained for precise control. An estimation process is required for both noisy gyro measurements and the time derivative of the gyro measurements. In this paper, an estimation method is proposed for having reliable estimates of inertia properties. First, the Euler equations of motion are reformulated to obtain a regressor matrix. Next, the extended Kalman filter is adopted to reduce the noise effects in gyro angular velocity measurements. Last, the inertia properties are estimated using linear least squares. To achieve reliable and accurate angular accelerations, a Savitzky-Golay filter based on an even number sampled data is utilized. Numerical examples are presented to demonstrate the performance of the proposed algorithm for the case of a space vehicle. The numerical simulation results show that the proposed algorithm provides accurate inertia property estimates in the presence of noisy measurements.
Avoidable Compartment Syndrome! High Index of Suspicion for a Newly Presenting Haemophiliac: A Case Series
Authors: Niblock A. , Donnelly K. , Sayers F. , Winter P. , Benson G.
Published: May 2016

Bleeding disorders can present at any age and vary in their severity. Haemophilia, which is characterised by its x-linked recessive inheritance, can present with a spontaneous mutation and therefore no family history will be evident. Three cases of trauma induced thigh haematomas as an initial presenting feature for people with haemophilia are discussed. The cases highlight the importance of a coagulation screen if the patients bleeding phenotype does not match the injury sustained. An isolated prolonged APTT with no offending anticoagulant cause should always be investigated to look for underlying haemophilia. Interestingly the cases demonstrate the limitations of a coagulation screen. Factor VIII being an acute phase reactant can result in the fact that the initial coagulation screen may be temporarily normal. Therefore, if there is a high index of suspicion for a bleeding disorder, consider repeating the coagulation screen and seeking haematology opinion. Early diagnosis and appropriate specific factor replacement for an injured haemophiliac prevent haematomas expanding thus avoiding potential complications like compartment syndrome or unnecessary surgical input.
Null Curve Evolution in Four-Dimensional Pseudo-Euclidean Spaces
Authors: del Amor José , Giménez Ángel , Lucas Pascual
Published: June 2016

We define a Lie bracket on a certain set of local vector fields along a null curve in a 4-dimensional semi-Riemannian space form. This Lie bracket will be employed to study integrability properties of evolution equations for null curves in a pseudo-Euclidean space. In particular, a geometric recursion operator generating infinitely many local symmetries for the null localized induction equation is provided.
Folic Acid Supplementation Mitigates Alzheimer’s Disease by Reducing Inflammation: A Randomized Controlled Trial
Authors: Chen Hui , Liu Shuai , Ji Lu , Wu Tianfeng , Ji Yong , Zhou Yuying , Zheng Miaoyan , Zhang Meilin , Xu Weili , Huang Guowei
Published: June 2016

Background/Aims. Low serum folate levels can alter inflammatory reactions. Both phenomena have been linked to Alzheimer’s disease (AD), but the effect of folic acid on AD itself is unclear. We quantified folate supplementation’s effect on inflammation and cognitive function in patients with AD over the course of 6 months.Methods. Patients newly diagnosed with AD (age > 60 years;n=121; mild to severe; international criteria) and being treated with donepezil were randomly assigned into two groups with (intervention group) or without (control group) supplemental treatment with folic acid (1.25 mg/d) for 6 months. The Mini-Mental State Examination (MMSE) was administered to all patients at baseline and follow-up, and blood samples were taken before and after treatment. We quantified serum folate, amyloid beta (Aβ), interleukin-6 (IL-6), tumor necrosis factorα(TNFα), plasma homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and the mRNA levels of presenilin (PS), IL-6, and TNFαin leukocytes. Data were analyzed using a repeated-measures mixed model.Results. The mean MMSE was slightly increased in the intervention group compared to that in the control group (P<0.05). Posttreatment, plasma SAM and SAM/SAH levels were significantly higher (P<0.05), while Aβ40, PS1-mRNA, and TNFα-mRNA levels were lower in the intervention group than in the control group (P<0.05). The Aβ42/Aβ40ratio was also higher in the intervention group (P<0.05).Conclusions. Folic acid is beneficial in patients with AD. Inflammation may play an important role in the interaction between folic acid and AD. This trial is registered with clinical trial registration numberChiCTR-TRC-13003246.
Functional Characteristics of Multipotent Mesenchymal Stromal Cells from Pituitary Adenomas
Authors: Megnis Kaspars , Mandrika Ilona , Petrovska Ramona , Stukens Janis , Rovite Vita , Balcere Inga , Jansone Laima Sabine , Peculis Raitis , Pirags Valdis , Klovins Janis
Published: June 2016

Pituitary adenomas are one of the most common endocrine and intracranial neoplasms. Although they are theoretically monoclonal in origin, several studies have shown that they contain different multipotent cell types that are thought to play an important role in tumor initiation, maintenance, and recurrence after therapy. In the present study, we isolated and characterized cell populations from seven pituitary somatotroph, nonhormonal, and lactotroph adenomas. The obtained cells showed characteristics of multipotent mesenchymal stromal cells as observed by cell morphology, cell surface marker CD90, CD105, CD44, and vimentin expression, as well as differentiation to osteogenic and adipogenic lineages. They are capable of growth and passaging under standard laboratory cell culture conditions and do not manifest any hormonal cell characteristics. Multipotent mesenchymal stromal cells are present in pituitary adenomas regardless of their clinical manifestation and show no considerable expression of somatostatin 1–5 and dopamine 2 receptors. Most likely obtained cells are a part of tissue‐supportive cells in pituitary adenoma microenvironment.
Enhancement of the Antibacterial Activity of Silver Nanoparticles against Phytopathogenic BacteriumRalstonia solanacearumby Stabilization
Authors: Chen Juanni , Li Shili , Luo Jinxiang , Wang Rongsheng , Ding Wei
Published: June 2016

In this paper, the enhanced antibacterial activity of silver nanoparticles (AgNPs) against the phytopathogenic bacteriumRalstonia solanacearumafter stabilization using selected surfactants (SDS, SDBS, TX-100, and Tween 80) was examined, in comparison with silver ion. Tween 80 was found to be the most preferable stabilizer of AgNPs due to the beneficial synergistic effects of the AgNPs and surfactant. However, all the surfactants nearly had no effects on the antibacterial activity of Ag+.In vitro, Tween 80-stabilized AgNPs showed the highest bactericidal activity againstR. solanacearum. Further measurements using TEM, fluorescence microscopy, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that though Ag+and Tween 80-Ag+induced high toxicity, Tween 80-stabilized AgNPs displayed most severe damage when in direct contact with cells, causing mechanistic injury to the cell membrane and strongly modifying and destructing the cellular proteins. Meanwhile,in vivo, the pot experiments data indicated that the control efficiency of Tween 80-stabilized AgNPs on tobacco bacterial wilt was 96.71%, 90.11%, and 84.21%, at 7 days, 14 days, and 21 days, respectively. Based on the results evidencing their advantageous low dosage requirements and strong antimicrobial activity, Tween 80-stabilized AgNPs are a promising antibacterial agent for use in alternative crop disease control approaches.
Increased Risk of Postthoracotomy Pain Syndrome in Patients with Prolonged Hospitalization and Increased Postoperative Opioid Use
Authors: Kinney Michelle A. O. , Jacob Adam K. , Passe Melissa A. , Mantilla Carlos B.
Published: June 2016

Background. Postthoracotomy pain syndrome (PTPS) is unfortunately very common following thoracotomy and results in decreased quality of life. The purpose of this retrospective study was to determine perioperative patient, surgical, and analgesic characteristics associated with the development of PTPS. Methods. Sixty-six patients who presented to the Mayo Clinic Rochester Pain Clinic were diagnosed with PTPS 2 months or more after thoracotomy with postoperative epidural analgesia. These patients were matched with sixty-six control patients who underwent thoracotomy with postoperative epidural analgesia and were never diagnosed with PTPS. Results. Median (IQR) hospital stay was significantly different between control patients (5 days (4, 6)) compared with PTPS patients (6 days (5, 8)), P<0.02. The total opioid equivalent utilized in oral morphine equivalents in milligrams for the first three days postoperatively was significantly different between control patients and PTPS patients. The median (IQR) total opioid equivalent utilized was 237 (73, 508) for controls and 366 (116, 874) for PTPS patients (P<0.005). Conclusion. Patients with a prolonged hospital stay after thoracotomy were at an increased risk of developing PTPS, and this is a novel finding. Patients who utilize higher oral morphine equivalents for the first 3 days were also at increased risk for PTPS.
Analysis of Dynamic Fracture Parameters in Functionally Graded Material Plates with Cracks by Graded Finite Element Method and Virtual Crack Closure Technique
Authors: Zhou Li Ming , Meng Guang Wei , Li Xiao Lin , Li Feng
Published: June 2016

Based on the finite element software ABAQUS and graded element method, we developed a dummy node fracture element, wrote the user subroutines UMAT and UEL, and solved the energy release rate component of functionally graded material (FGM) plates with cracks. An interface element tailored for the virtual crack closure technique (VCCT) was applied. Fixed cracks and moving cracks under dynamic loads were simulated. The results were compared to other VCCT-based analyses. With the implementation of a crack speed function within the element, it can be easily expanded to the cases of varying crack velocities, without convergence difficulty for all cases. Neither singular element nor collapsed element was required. Therefore, due to its simplicity, the VCCT interface element is a potential tool for engineers to conduct dynamic fracture analysis in conjunction with commercial finite element analysis codes.
Breast Metastasis in Esophagus Cancer: Literature Review and Report on a Case
Authors: Ghibour Abdulaziz , Shaheen Osama
Published: May 2016

Esophagus cancer metastases often involve locoregional lymph nodes, lung, bone, liver, and brain. Metastatic involvement of the breast from esophagus cancer is uncommon, but if it happened, it usually presents as a part of multiple organ distal metastases. Here we report a case of the largest metastatic esophagus cancer of the breast and the chest wall, and we review the similar reported cases.
A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice
Authors: Liu Mi , Jia Zhanjun , Sun Ying , Zhang Aihua , Yang Tianxin
Published: May 2016

Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1βin circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS) and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response.
Validation of the Turkish Version of the Rapid Eye Movement Sleep Behavior Disorder Questionnaire
Authors: Tarı Cömert Itır , Pelin Zerrin , Arıcak Tolga , Yapan Saadet
Published: June 2016

The aim of this study was to assess the validity and reliability of a Turkish version of the rapid eye movement sleep behavior disorder questionnaire (the RBDSQ-T) for identifying patients with rapid eye movement sleep behavior disorder (RBD) and to ensure that this tool can be applied in Turkish language. Three groups were enrolled to validate the RBDSQ-T: 78 healthy controls, 17 patients previously diagnosed with RBD, and 28 patients with obstructive sleep apnea syndrome (OSAS). Based on a cut-off score of five, the RBDSQ-T was able to discriminate RBD patients from healthy controls with sensitivity of 100% and specificity of 87%. Accordingly, 63% of patients were correctly diagnosed using the RBDSQ-T. Similarly, with a cut-off score of five, the RBDSQ-T was able to discriminate RBD from OSAS with sensitivity of 100% and specificity of 64%. Assessment of test-retest reliability and internal consistency reliability using Kuder-Richardson 20 analysis revealed a test-retest correlation coefficient of 0.95 and a Kuder-Richardson 20 value of 0.82. The findings demonstrate that the RBDSQ-T is a valid and reliable tool.
High CDK6 Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor–Positive Metastatic Breast Cancer
Authors: Alves Carla L. , Elias Daniel , Lyng Maria , Bak Martin , Kirkegaard Tove , Lykkesfeldt Anne E. , Ditzel Henrik J.
Published: June 2016

Purpose: Resistance to endocrine therapy in estrogen receptor–positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole or fulvestrant was approved for treatment of ER+ advanced breast cancer. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined.

Experimental Design: We investigated the specific role of increased CDK6 expression in fulvestrant-resistant cells by gene knockdown and treatment with palbociclib, and evaluated the effect in cell proliferation, apoptosis, and kinase activity. Furthermore, we evaluated CDK6 expression in metastatic samples from breast cancer patients treated or not with fulvestrant.

Results: We found increased expression of CDK6 in two fulvestrant-resistant cell models versus sensitive cells. Reduction of CDK6 expression impaired fulvestrant-resistant cell growth and induced apoptosis. Treatment with palbociclib resensitized fulvestrant-resistant cells to fulvestrant through alteration of retinoblastoma protein phosphorylation. High CDK6 levels in metastatic samples from two independent cohorts of breast cancer patients treated with fulvestrant (N = 45 and 46) correlated significantly with shorter progression-free survival (PFS) on fulvestrant treatment (P = 0.0006 and 0.018), whereas no association was observed in patients receiving other first- or second-/third-line endocrine treatments (N = 68, P = 0.135 and 0.511, respectively).

Conclusions: Our results indicate that upregulation of CDK6 may be an important mechanism in overcoming fulvestrant-mediated growth inhibition in breast cancer cells. Patients with advanced ER+ breast cancer exhibiting high CDK6 expression in the metastatic lesions show shorter PFS upon fulvestrant treatment and thus may benefit from the addition of CDK4/6 inhibitors in their therapeutic regimens. Clin Cancer Res; 22(22); 5514–26. ©2016 AACR.
Synchronized Nasal Intermittent Positive Pressure Ventilation of the Newborn: Technical Issues and Clinical Results
Authors: Moretti Corrado , Gizzi Camilla , Montecchia Francesco , Barbàra Caterina Silvia , Midulla Fabio , Sanchez-Luna Manuel , Papoff Paola
Published: June 2016

Although mechanical ventilation via an endotracheal tube has undoubtedly led to improvement in neonatal survival in the last 40 years, the prolonged use of this technique may predispose the infant to development of many possible complications including bronchopulmonary dysplasia. Avoiding mechanical ventilation is thought to be a critical goal, and different modes of noninvasive respiratory support beyond nasal continuous positive airway pressure, such as nasal intermittent positive pressure ventilation and synchronized nasal intermittent positive pressure ventilation, are also available and may reduce intubation rate. Several trials have demonstrated that the newer modes of noninvasive ventilation are more effective than nasal continuous positive airway pressure in reducing extubation failure and may also be more helpful as modes of primary support to treat respiratory distress syndrome after surfactant and for treatment of apnea of prematurity. With synchronized noninvasive ventilation, these benefits are more consistent, and different modes of synchronization have been reported. Although flow-triggering is the most common mode of synchronization, this technique is not reliable for noninvasive ventilation in neonates because it is affected by variable leaks at the mouth and nose. This review discusses the mechanisms of action, benefits and limitations of noninvasive ventilation, describes the different modes of synchronization and analyzes the technical characteristics, properties and clinical results of a flow-sensor expressly developed for synchronized noninvasive ventilation.
Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis
Authors: Ye Fang , Luo Yong-Jie , Xiao Jun , Yu Neng-Wei , Yi Gang
Published: June 2016

Background: Abundant evidence from epidemiological and clinical studies has proven that diabetes mellitus (DM) is correlated with an increased incidence of dementia and Alzheimer's disease (AD). Insulin resistance is considered to play an important role in the associations between DM and dementia. However, whether insulin sensitizer drugs are effective in preventing dementia still remains unclear. Methods: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies that reported about the associations between insulin sensitizers and the incidence of dementia. The included studies were reviewed, and a meta-analysis was performed using STATA to determine the combined relative risk (RR) for the incidence of dementia when using insulin sensitizers. Subgroup analysis and meta regression were also conducted. Results: In total, nine comparisons out of six studies were qualified for inclusion, and data from 544,093 participants were evaluated. The results of the meta-analysis revealed a combined RR of 0.78 (95% CI 0.64-0.95, p = 0.015) for the incidence of dementia when using insulin sensitizers. The incidence rate of dementia was reduced with either metformin (RR 0.79, 95% CI 0.62-1.01, p = 0.064) or thiazolidinediones (RR 0.75, 95% CI 0.56-1.00, p = 0.050), both with a marginal trend toward significance. Conclusions: The results indicate that insulin sensitizer drugs might provide protection against incident dementia. Controlled studies with large samples should be conducted to further confirm these conclusions and provide information for clinical strategies.
Gastric Cancer Patients with High PLK1 Expression and DNA Aneuploidy Correlate with Poor Prognosis
Authors: Otsu Hajime , Iimori Makoto , Ando Koji , Saeki Hiroshi , Aishima Shinichi , Oda Yoshinao , Morita Masaru , Matsuo Keitaro , Kitao Hiroyuki , Oki Eiji , Maehara Yoshihiko
Published: June 2016

Gastric cancer is the fourth most common cancer worldwide. Although it is important to identify patients at high risk for a poor outcome, factors correlating with prognosis in gastric cancer are largely unknown. Here, we focus on the correlations among expression of Polo-like kinase 1 (PLK1), DNA ploidy, and clinical outcome in gastric cancer patients. Gastric cancer specimens were analyzed from 207 consecutive patients. Patients were classified into two groups according to tumor PLK1 expression and DNA content, and an analysis of their clinical outcomes was carried out. Prognoses of patients with PLK1-high tumors were worse than those of patients with PLK1-low tumors, but the differences were not statistically significant. In cell lines, overexpression of PLK1 induced centrosome amplification and multipolar spindles, potentially leading to DNA aneuploidy. Indeed, high expression of PLK1 was also associated with DNA aneuploidy in clinical gastric cancer specimens. Patients with both high PLK1 expression and DNA aneuploidy had poor recurrence-free survival, whereas PLK1 expression and DNA ploidy status alone were not significantly associated with outcome. Here, we provide clinical evidence that high expression of PLK1 could have detrimental effects in tumors with DNA aneuploidy, which may increase the risk of recurrence in gastric cancer patients.
Sex-Based Differences in Smgc Expression in the Submandibular Gland of C57BL/6 Mice
Authors: Kusakabe Yuko , Shindo Yumiko , Kawai Takayuki , Takahashi Yoko , Kobori Masuko , Inoue Hiroko , Saito Ichiro
Published: June 2016

Objective: The decrease in female hormone levels at menopause affects whole-body homeostasis. Various therapies including hormone therapy and treatment with herbal supplements are available to improve menopausal symptoms. However, a method for evaluating their effectiveness has not been established. We sought to identify useful biomarkers to assess therapy efficacy. Methods: We searched for salivary proteins affected by changes in female hormone levels in mouse submandibular glands. Results: The expression of submandibular gland protein C (Smgc) was decreased following ovariectomy, while the expression of the alternative splicing transcript t-Smgc was increased. Notably, Smgc expression increased following β-estradiol administration, and was barely detectable in the submandibular glands of male mice. Conclusion: The results suggest that Smgc expression may be estrogen dependent. Moreover, changes in the SMGC protein amount in the saliva were in accordance with those in mRNA expression in the submandibular gland. Our findings suggest that salivary proteins have potential as markers for evaluating therapies for menopausal symptoms.
Z-Score Reference Ranges for Angular M-Mode Displacement at 22-40 Weeks' Gestation
Authors: Mao Yan-Kai , Zhao Bo-Wen , Wang Bei
Published: June 2016

Objectives: To construct Z-score reference ranges for fetal mitral and tricuspid annular plane systolic excursions (MAPSE and TAPSE), using angular M-mode (AM) and conventional M-mode (CM). Methods: A prospective cross-sectional investigation was conducted on 261 normal singleton fetuses from 22 to 40 weeks' gestation. TAPSE and MAPSE were measured by AM and CM. Reference ranges of TAPSE and MAPSE derived from AM and CM were determined against gestational age (GA) and heart area (HA), using regression analyses of the mean and standard deviation. Results: TAPSE and MAPSE showed positive correlations with GA and HA. A cubic regression was the best-fitted model for the mean of MAPSE and TAPSE based on HA, while a linear regression model was established for the mean based on GA. Z-scores and 95% reference intervals for predicting MAPSE and TAPSE were established. Strong correlations were found between AM and CM, whereas CM underestimated AM (mean error: MAPSE 0.25 ± 0.18 mm; TAPSE 0.35 ± 0.2 mm). Conclusion: Normal data and the Z-scores of fetal MAPSE and TAPSE were provided against GA and HA, which can be useful for quantitative assessment of fetal cardiac dysfunction, particularly in cases of intrauterine growth restriction.
Free-Floating, Pigmented Cysts in the Anterior Chamber Causing Ocular Hypertension
Authors: Maslin Jessica S. , Teng Christopher C. , Materin Miguel
Published: June 2016

Purpose: The aim of this study was to describe the clinical and histopathological features of a 36-year-old male with hundreds of recurrent, unilateral, free-floating, pigmented cysts in the anterior chamber causing ocular hypertension. Procedures: The patient was referred to ocular oncology for blurry vision of the right eye and was found to have myriad pigmented, free-floating cysts in the anterior chamber and heavy pigmentation of the angle on gonioscopy. Anterior chamber washout was performed, and the fluid recovered was sent for pathological analysis. Results: The pathology report demonstrated rare nonpigmented epithelial cells, more consistent with iris stromal cysts or secondary implantation epithelial cysts. Conclusions: This paper highlights the first documented case of innumerable spontaneously occurring, unilateral, free-floating, pigmented cysts in the anterior chamber. While clinical diagnosis suggested iris pigment epithelial cysts, pathology suggested iris stromal cysts or secondary implantation epithelial cysts.
Prediction of Postoperative Complications Following Elective Surgery in Elderly Patients with Colorectal Cancer Using the Comprehensive Geriatric Assessment
Authors: Mokutani Yukako , Mizushima Tsunekazu , Yamasaki Makoto , Rakugi Hiromi , Doki Yuichiro , Mori Masaki
Published: June 2016

Aims: The study aims to determine whether the Comprehensive Geriatric Assessment (CGA) could predict complications of colorectal cancer (CRC) surgery and identify the problems. So we compared the prognostic value of the CGA with patient characteristics and determined predictive scores. Methods: A total of 156 patients aged 75 years and older, who underwent surgery for CRC at Osaka University Hospital, were enrolled. Each patient was examined by the CGA prospectively, and all postoperative complications were obtained from the medical records. The CGA included the Barthel Index (BI), Vitality Index, instrumental activities of daily living (iADL), Mini-Mental State Examination (MMSE) and Geriatric Depression Score (GDS). All elements were retrospectively compared in patients with or without postoperative complications, including delirium, surgical site infection and ileus. Results: Overall, postoperative complications developed in 76 patients (48.7%). The BI and MMSE were associated with the incidence of complications, and BI, iADL, MMSE and GDS were significantly related with delirium. Multivariate logistic analysis identified the MMSE as a significant determinant of postoperative complications after adjusting for other determined predictive scores including the prognostic nutritional index and performance status. Conclusion: The CGA was a useful predictor of postoperative complications in elderly patients when administered before surgery for CRC.
Endothelial RAGE exacerbates acute postischaemic cardiac inflammation
Authors: Ziegler Tilman , Horstkotte Melanie , Lange Philipp , Ng Judy , Bongiovanni Dario , Hinkel Rabea , Laugwitz Karl-Ludwig , Sperandio Markus , Horstkotte Jan , Kupatt Christian
Published: June 2016

Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 ± 4 cells/ hpf) was significantly reduced in ICAM-1-/- (40 ± 3 cells/hpf) and RAGE-/- mice (38 ± 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 ± 3 cells/ hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28%), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55%). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 ± 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/- BM) leucocyte retention was significantly reduced (13 ± 1 cells/hpf), similar to non-transplanted ICAM/ RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 ± 4 mmHg vs 86 ± 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion. RAGE represents an additional pro-inflammatory endothelial mediator of ischaemia-reperfusion injury.