bluuebunny/crossref_metadata_2025 huggingface dataset:
ASK1 mediates the teratogenicity of diabetes in the developing heart by inducing ER stress and inhibiting critical factors essential for cardiac development
Authors: Wang Fang , Wu Yanqing , Quon Michael J. , Li Xuezheng , Yang Peixin
Published: July 2015

Maternal diabetes in mice induces heart defects similar to those observed in human diabetic pregnancies. Diabetes enhances apoptosis and suppresses cell proliferation in the developing heart, yet the underlying mechanism remains elusive. Apoptosis signal-regulating kinase 1 (ASK1) activates the proapoptotic c-Jun NH2-terminal kinase 1/2 (JNK1/2) leading to apoptosis, suggesting a possible role of ASK1 in diabetes-induced heart defects. We aimed to investigate whether ASK1 is activated in the heart and whether deleting the Ask1 gene blocks diabetes-induced adverse events and heart defect formation. The ASK1-JNK1/2 pathway was activated by diabetes. Deleting Ask1 gene significantly reduced the rate of heart defects, including ventricular septal defects (VSDs) and persistent truncus arteriosus (PTA). Additionally, Ask1 deletion diminished diabetes-induced JNK1/2 phosphorylation and its downstream transcription factors and endoplasmic reticulum (ER) stress markers. Consistent with this, caspase activation and apoptosis were blunted. Ask1 deletion blocked the increase in cell cycle inhibitors (p21 and p27) and the decrease in cyclin D1 and D3 and reversed diabetes-repressed cell proliferation. Ask1 deletion also restored the expression of BMP4, NKX2.5, and GATA5, Smad1/5/8 phosphorylation, whose mutations or deletion result in reduced cell proliferation, VSD, and PTA formation. We conclude that ASK1 may mediate the teratogenicity of diabetes through activating the JNK1/2-ER stress pathway and inhibiting cell cycle progression, thereby impeding the cardiogenesis pathways essential for ventricular septation and outflow tract development.
Integrated microRNA and mRNA responses to acute human left ventricular ischemia
Authors: Saddic Louis A. , Chang Tzuu-Wang , Sigurdsson Martin I. , Heydarpour Mahyar , Raby Benjamin A. , Shernan Stanton K. , Aranki Sary F. , Body Simon C. , Muehlschlegel Jochen D.
Published: July 2015

MicroRNAs (miRNAs) play a significant role in ischemic heart disease. Animal models of left ventricular (LV) ischemia demonstrate a unique miRNA profile; however, these models have limitations in describing human disease. In this study, we performed next-generation miRNA and mRNA sequencing on LV tissue from nine patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. Samples were obtained immediately after aortic cross clamping (baseline) and before aortic cross clamp removal (postischemic). Of 1,237 identified miRNAs, 21 were differentially expressed between baseline and postischemic LV samples including the upregulated miRNAs miR-339-5p and miR-483-3p and the downregulated miRNA miR-139-5p. Target prediction analysis of these miRNAs was integrated with mRNA expression from the same LV samples to identify anticorrelated miRNA-mRNA pairs. Gene enrichment studies of candidate mRNA targets demonstrated an association with cardiovascular disease, cell death, and metabolism. Therapeutics that intervene on these miRNAs and their downstream targets may lead to novel mechanisms of mitigating the damage caused by ischemic insults on the human heart.
Infusion of Sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate-Conjugated MOG35–55-Coupled Spleen Cells Effectively Prevents and Reverses Experimental Autoimmune Encephalomyelitis in Mice
Authors: Zhang Lanfang , Guo Yixian , Xia Chang-Qing
Published: July 2015

In this study, we have evaluated our recently developed method for antigen-cell coupling using sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) heterobifunctional crosslinker in prevention and reversal of experimental autoimmune encephalomyelitis (EAE). We demonstrate that infusion of MOG35–55-coupled spleen cells (MOG-SP) significantly prevents and reverses EAE. Further studies show that the protected animals exhibit significantly delayed EAE upon EAE reinduction. Moreover, adoptive transfer of CD4+ T cells from the protected mice to naïve syngeneic mice renders the recipient mice resistant to EAE induction. Unexpectedly, CD4+ T cell proliferation is similar upon ex vivo stimulation by MOG35–55amongst all groups. However, further analysis of those proliferating CD4+ T cells shows remarkable differences in Foxp3+ regulatory T cells (70% in MOG-SP groups versus 10–25% in control groups) and in IL-17+ cells (2-3% in MOG-SP groups versus 6–9% in control groups). In addition, we discover that MOG-SP treatment also significantly attenuates MOG35–55-responding IFN-γ-producing Th1 cells. These findings suggest that MOG-SP treatment induces EAE protective MOG35–55-specific regulatory T cells and suppresses EAE pathogenic Th17 and Th1 cells. Our study provides a novel approach for antigen-based EAE immunotherapy, which can potentially be translated into clinical application for immunotherapy of multiple sclerosis.
Antigenotoxic Effect of Trametes spp. Extracts against DNA Damage on Human Peripheral White Blood Cells
Authors: Knežević Aleksandar , Živković Lada , Stajić Mirjana , Vukojević Jelena , Milovanović Ivan , Spremo-Potparević Biljana
Published: July 2015

Trametes species have been used for thousands of years in traditional and conventional medicine for the treatment of various types of diseases. The goal was to evaluate possible antigenotoxic effects of mycelium and basidiocarp extracts of selected Trametes species and to assess dependence on their antioxidant potential. Trametes versicolor, T. hirsuta, and T. gibbosa were the species studied. Antigenotoxic potentials of extracts were assessed on human peripheral white blood cells with basidiocarp and mycelium extracts of the species. The alkaline comet test was used for detection of DNA strand breaks and alkali‐labile sites, as well as the extent of DNA migration. DPPH assay was used to estimate antioxidative properties of extracts. Fruiting body extracts of T. versicolor and T. gibbosa as well as T. hirsuta extracts, except that at 20.0 mg/mL, were not genotoxic agents. T. versicolor extract had at 5.0 mg/mL the greatest antigenotoxic effect in both pre‐ and posttreatment of leukocytes. The mycelium extracts of the three species had no genotoxic activity and significant antigenotoxic effect against H2O2‐induced DNA damage, both in pre‐ and posttreatment. The results suggest that extracts of these three species could be considered as strong antigenotoxic agents able to stimulate genoprotective response of cells.
An Unusual Case:SalmonellaUTI and Orchitis in HIV Patient
Authors: Arshed Sabrina , Luo Hongxiu , Middleton John , Yousif Abdalla
Published: July 2015

Salmonellosis is a major cause of gastroenteritis in the United States; however, nontyphoidal strains ofSalmonellahave also been known to cause urinary tract infections, usually transmitted via the fecal-urethral route. This can lead to critical illness in those patients with immune deficiencies, especially HIV, cancer patients, and those with diabetes mellitus. However, the spread of the infection from the urinary tract to involve the testicles and epididymis is very rare. Here, we present the first documented case of an immune-compromised young male with a urinary tract infection with orchitoepididymitis.
Subdivision Schemes Based Collocation Algorithms for Solution of Fourth Order Boundary Value Problems
Authors: Ejaz Syeda Tehmina , Mustafa Ghulam , Khan Faheem
Published: July 2015

We present two collocation algorithms based on interpolating and approximating subdivision schemes for the solution of fourth order boundary value problems arising in the mathematical modeling of viscoelastic, and inelastic flows, deformation of beams, arches, and load bearing members like street lights and robotic arms in multipurpose engineering systems. Numerical examples are given to illustrate the algorithms. We conclude that approximating schemes based collocation algorithms give better solution than interpolating schemes based collocation algorithms. Main purpose of this paper is to explore and seek the applications of interpolating and approximating subdivision schemes in the field of boundary value problems along with intrinsic comparison of the results obtained by algorithms based on these schemes. A comparison with other approaches of this type of boundary value problems in order to see the advantages of the proposed methods is also given.
Stability Analysis of One-Leg Methods for Nonlinear Neutral Delay Integrodifferential Equations
Authors: Yu Yuexin , Wen Liping
Published: July 2015

This paper is concerned with the numerical solution of nonlinear neutral delay integrodifferential equations (NDIDEs). The adaptation of one-leg methods is considered. It is proved that anA-stable one-leg method can preserve the global stability and a stronglyA-stable one-leg method can preserve the asymptotic stability of the analytical solution of nonlinear NDIDEs. Numerical tests are given to confirm the theoretical results.
Social Attitudes toward Cerebral Palsy and Potential Uses in Medical Education Based on the Analysis of Motion Pictures
Authors: Jóźwiak Marek , Chen Brian Po-Jung , Musielak Bartosz , Fabiszak Jacek , Grzegorzewski Andrzej
Published: July 2015

This study presents how motion pictures illustrate a person with cerebral palsy (CP), the social impact from the media, and the possibility of cerebral palsy education by using motion pictures. 937 motion pictures were reviewed in this study. With the criteria of nondocumentary movies, possibility of disability classification, and availability, the total number of motion pictures about CP was reduced to 34. The geographical distribution of movie number ever produced is as follows: North America 12, Europe 11, India 2, East Asia 6, and Australia 3. The CP incidences of different motor types in real world and in movies, respectively, are 78–86%, 65% (Spastic); 1.5–6%, 9% (Dyskinetic); 6.5–9%, 26% (Mixed); 3%, 0% (Ataxic); 3-4%, 0% (Hypotonic). The CP incidences of different Gross Motor Function Classification System (GMFCS) levels in real world and in movies, respectively, are 40–51%, 47% (Level I + II); 14–19%, 12% (Level III); 34–41%, 41% (Level IV + V). Comparisons of incidence between the real world and the movies are surprisingly matching. Motion pictures honestly reflect the general public’s point of view to CP patients in our real world. With precise selection and medical professional explanations, motion pictures can play the suitable role making CP understood more clearly.
Cell-Based Smoothed Finite Element Method-Virtual Crack Closure Technique for a Piezoelectric Material of Crack
Authors: Zhou Li Ming , Meng Guang Wei , Li Feng , Wang Hui
Published: July 2015

In order to improve the accuracy and efficiency of solving fracture parameters of piezoelectric materials, a piezoelectric element, tailored for the virtual crack closure technique (VCCT), was used to study piezoelectric materials containing a crack. Recently, the cell-based smoothed finite element method (CSFEM) and VCCT have been used to simulate the fracture mechanics of piezoelectric materials. A center cracked piezoelectric materials with different material properties, crack length, mesh, and smoothing subcells at various strain energy release rates are discussed and compared with finite element method-virtual crack closure technique (FEM-VCCT). Numerical examples show that CSFEM-VCCT gives an improved simulation compared to FEM-VCCT, which generally simulates materials as too stiff with lower accuracy and efficiency. Due to its simplicity, the VCCT piezoelectric element demonstrated in this study could be a potential tool for engineers to practice piezoelectric fracture analysis. CSFEM-VCCT is an efficient numerical method for fracture analysis of piezoelectric materials.
Evaluation of Extraradicular Diffusion of Hydrogen Peroxide during Intracoronal Bleaching Using Different Bleaching Agents
Authors: Rokaya Mohammad E. , Beshr Khaled , Hashem Mahram Abeer , Samir Pedir Samah , Baroudi Kusai
Published: July 2015

Objectives. Extra radicular diffusion of hydrogen peroxide associated with intracoronal teeth bleaching was evaluated.Methods. 108 intact single rooted extracted mandibular first premolars teeth were selected. The teeth were instrumented with WaveOne system and obturated with gutta percha and divided into four groups (n=27) according to the bleaching materials used. Each main group was divided into three subgroups (n=9) according to the time of extra radicular hydrogen peroxide diffusion measurements at 1, 7, and 14 days: group 1 (35% hydrogen peroxide), group 2 (35% carbamide peroxide), group 3 (sodium perborate-30% hydrogen peroxide mixture), and group 4 (sodium perborate-water mixture). Four cemental dentinal defects were prepared just below the CEJ on each root surface. The amount of hydrogen peroxide that leached out was evaluated after 1, 7, and 14 days by spectrophotometer analysis. The results were analyzed using the ANOVA and Tukey’s test.Results. Group 1 showed highest extra radicular diffusion, followed by group 3 and group 2, while group 4 showed the lowest mean extra radicular diffusion.Conclusion. Carbamide peroxide and sodium perborate-water mixture are the most suitable bleaching materials used for internal bleaching due to their low extra radicular diffusion of hydrogen peroxide.
Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation inCDKN1B
Authors: Elston Marianne S. , Meyer-Rochow Goswin Y. , Dray Michael , Swarbrick Michael , Conaglen John V.
Published: July 2015

Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes:MEN1, CASR, orCDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations inCDKN1Band those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novelCDKN1Bgermline mutation (heterozygote for a missense mutation in exon 1 of theCDKN1Bgene (c.378G>C) (p.E126D)). The implication from this case is thatCDKN1Bgermline mutations may be associated with PHPT at an earlier age than previously thought.
Brewers’ Rice: A By-Product from Rice Processing Provides Natural Hepatorenal Protection in Azoxymethane-Induced Oxidative Stress in Rats
Authors: Tan Bee Ling , Norhaizan Mohd Esa , Hairuszah Ithnin , Hazilawati Hamzah , Roselina Karim
Published: July 2015

Brewers’ rice, which is known locally astemukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers’ rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers’ rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers’ rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers’ rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers’ rice could be used in future applications to combat liver and kidney disease.
Stress Analysis of Rotary Vibration of Rigid Friction Pile and Stress General Solution of Central Symmetry Plane Elastic Problem
Authors: Zhao Fu-yao , Song Er-xiang , Yang Jun
Published: July 2015

The rotary vibration of rigid friction pile can be seen approximately as a central symmetry plane problem in elasticity. The stress general solution of central symmetry plane problem in elasticity can be constructed by technique such as the Laurent expansion of the volume force. This solution has some decoupling, generalized, and convergent properties, and it can be used in stress analysis of the rotary vibration of pile. The analysis results show that the maximum value of displacement will not occur at the edge of the pile and the assumption that pile cross section remains unchanged is no longer applicable, if the value of one dimensionless quantity, reflecting the angular frequency of the rotation, radius, and material properties of the pile, is larger than 1.84. Once the rotary vibration of rigid friction pile happens, the pile may lose its bearing capacity under the comprehensive effect of normal and shear stress of the pile-soil interface and it will be very difficult to recover.
Recent Advances of Amorphous Wire CMOS IC Magneto-Impedance Sensors: Innovative High-Performance Micromagnetic Sensor Chip
Authors: Mohri Kaneo , Uchiyama Tsuyoshi , Panina Larissa V. , Yamamoto Michiharu , Bushida Kenichi
Published: July 2015

We analyzed and organized the reasons why the amorphous wire CMOS IC magneto-impedance sensor (MI sensor) has rapidly been mass-produced as the electronic compass chips for the smart phones, mobile phones, and the wrist watches. Comprehensive advantageous features regarding six terms of (1) microsizing and ultralow power consumption, (2) high linearity without any hysteresis for the magnetic field detection, (3) high sensitivity for magnetic field detection with a Pico-Tesla resolution, (4) quick response for detection of magnetic field, (5) high temperature stability, and (6) high reversibility against large disturbance magnetic field shock are based on the magneto-impedance effect in the amorphous wires. We have detected the biomagnetic field using the Pico-Tesla resolution MI sensor at the room temperature such as the magneto-cardiogram (MCG), the magneto-encephalogram (MEG), and the self-oscillatory magnetic field of guinea-pig stomach smooth muscles (in vitro) that suggest the origin of the biomagnetic field is probably pulsive flow of Ca2+through the muscle cell membrane.
The Reduction of Modal Sensor Channels through a Pareto Chart Methodology
Authors: Lemler Kaci J. , Semke William H.
Published: July 2015

Presented herein is a new experimental sensor placement procedure developed to assist in placing sensors in key locations in an efficient method to reduce the number of channels for a full modal analysis. It is a fast, noncontact method that uses a laser vibrometer to gather a candidate set of sensor locations. These locations are then evaluated using a Pareto chart to obtain a reduced set of sensor locations that still captures the motion of the structure. The Pareto chart is employed to identify the points on a structure that have the largest reaction to an input excitation and thus reduce the number of channels while capturing the most significant data. This method enhances the correct and efficient placement of sensors which is crucial in modal testing. Previously this required the development and/or use of a complicated model or set of equations. This new technique is applied in a case study on a small unmanned aerial system. The test procedure is presented and the results are discussed.
Severe Hyperthyroidism Presenting with Acute ST Segment Elevation Myocardial Infarction
Authors: Zhou Dayan , Qu Zongjie , Wang Hao , Wang Zhe , Xu Qiang
Published: July 2015

Introduction. Acute myocardial infarction is life-threatening. A cardiac troponin rise accompanied by typical symptoms, ST elevation or depression is diagnostic of acute myocardial infarction. Here, we report an unusual case of a female who was admitted with chest pain. However, she did not present with a typical profile of an acute myocardial infarction patient.Case Presentation. A 66-year-old Han nationality female presented with chest pain. The electrocardiogram (ECG) revealed arched ST segment elevations and troponin was elevated. However, the coronary angiography showed a normal coronary arterial system. Thyroid function tests showed that this patient had severe hyperthyroidism.Conclusion. Our case highlights the possibility that hyperthyroidism may cause a large area of myocardium injury and ECG ST segment elevation. We suggest routine thyroid function testing in patients with chest pain.
Effect of Cinnamon Tea on Postprandial Glucose Concentration
Authors: Bernardo Maria Alexandra , Silva Maria Leonor , Santos Elisabeth , Moncada Margarida Maria , Brito José , Proença Luis , Singh Jaipaul , de Mesquita Maria Fernanda
Published: July 2015

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p< 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained fromC. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period.
Numerical Solutions for the Eighth-Order Initial and Boundary Value Problems Using the Second Kind Chebyshev Wavelets
Authors: Xu Xiaoyong , Zhou Fengying
Published: July 2015

A collocation method based on the second kind Chebyshev wavelets is proposed for the numerical solution of eighth-order two-point boundary value problems (BVPs) and initial value problems (IVPs) in ordinary differential equations. The second kind Chebyshev wavelets operational matrix of integration is derived and used to transform the problem to a system of algebraic equations. The uniform convergence analysis and error estimation for the proposed method are given. Accuracy and efficiency of the suggested method are established through comparing with the existing quintic B-spline collocation method, homotopy asymptotic method, and modified decomposition method. Numerical results obtained by the present method are in good agreement with the exact solutions available in the literatures.
CD38 in Hairy Cell Leukemia Is a Marker of Poor Prognosis and a New Target for Therapy
Authors: Poret Nicolas , Fu Qiangwei , Guihard Soizic , Cheok Meyling , Miller Katie , Zeng Gordon , Quesnel Bruno , Troussard Xavier , Galiègue-Zouitina Sylvie , Shelley Carl Simon
Published: July 2015

Hairy cell leukemia (HCL) is characterized by underexpression of the intracellular signaling molecule RhoH. Reconstitution of RhoH expression limits HCL pathogenesis in a mouse model, indicating this could represent a new therapeutic strategy. However, while RhoH reconstitution is theoretically possible as a therapy, it is technically immensely challenging as an appropriately functional RhoH protein needs to be specifically targeted. Because of this problem, we sought to identify druggable proteins on the HCL surface that were dependent upon RhoH underexpression. One such protein was identified as CD38. Analysis of 51 HCL patients demonstrated that 18 were CD38-positive. Interrogation of the clinical record of 23 relapsed HCL patients demonstrated those that were CD38-positive had a mean time to salvage therapy 71 months shorter than patients who were CD38-negative. Knockout of the CD38 gene in HCL cells increased apoptosis, inhibited adherence to endothelial monolayers, and compromised ability to produce tumors in vivo. Furthermore, an anti-CD38 antibody proved effective against pre-existing HCL tumors. Taken together, our data indicate that CD38 expression in HCL drives poor prognosis by promoting survival and heterotypic adhesion. Our data also indicate that CD38-positive HCL patients might benefit from treatments based on CD38 targeting. Cancer Res; 75(18); 3902–11. ©2015 AACR.
Hepatitis C Virus Seroprevalence in Mongolian Women Assessed by a Novel Multiplex Antibody Detection Assay
Authors: Dondog Bolormaa , Schnitzler Paul , Michael Kristina M. , Clifford Gary , Franceschi Silvia , Pawlita Michael , Waterboer Tim
Published: July 2015

Background: Hepatitis C virus (HCV) infection causes hepatocellular carcinoma and is an important cause of mortality in both industrialized and developing countries. We developed a single-step high-throughput multiplex serology assay for HCV antibody detection and determined HCV prevalence in a highly endemic country.

Methods: Five proteins (Core, NS3, NS4A, NS5A, NS5B) each from the three most common subtypes of HCV (1a, 1b, 2a) were recombinantly expressed and used as antigens in a multiplexed antibody detection assay. Multiplex HCV serology was validated with 432 reference sera whose HCV status was established by commercial ELISA, Western blot, and RNA assays. HCV antibodies were determined in 1,023 sera representative for the adult female population of Mongolia.

Results: In reference sera, detection of HCV (mostly Core and NS3) antibodies by multiplex serology showed 100% sensitivity and 99.6% specificity, and was in very good agreement with the commercial diagnostic assays (kappa, 0.96; 95% confidence interval, 0.92–0.99). The role of antibodies to NS4 and NS5 remains to be evaluated. In Mongolia, overall HCV antibody prevalence was 18.9% (17.8% when age-standardized to the world population). HCV seroprevalence increased with age from 10% in women <30 years to 32% in women ≥50 years, but was not related to sexual risk factors.

Conclusions: The single-step high-throughput multiplex HCV serology assay performs similarly to conventional HCV antibody screening followed by secondary confirmation assays. A very high HCV seroprevalence was confirmed across all socio-economic groups in the female population of Mongolia.

Impact: Multiplex HCV serology facilitates large seroepidemiologic studies of HCV infection. Cancer Epidemiol Biomarkers Prev; 24(9); 1360–5. ©2015 AACR.
Robust In Vitro and In Vivo Neutralization against Multiple High-Risk HPV Types Induced by a Thermostable Thioredoxin-L2 Vaccine
Authors: Seitz Hanna , Ribeiro-Müller Lis , Canali Elena , Bolchi Angelo , Tommasino Massimo , Ottonello Simone , Müller Martin
Published: July 2015

Current prophylactic virus-like particle (VLP) human papillomavirus (HPV) vaccines are based on the L1 major capsid protein and provide robust but virus type-restricted protection. Moreover, VLP vaccines have a high production cost, require cold-chain storage, and are thus not readily implementable in developing countries, which endure 85% of the cervical cancer–related death burden worldwide. In contrast with L1, immunization with minor capsid protein L2 elicits broad cross-neutralization, and we previously showed that insertion of a peptide spanning amino acids 20–38 of L2 into bacterial thioredoxin (Trx) greatly enhances its immunogenicity. Building on this finding, we use, here, four different neutralization assays to demonstrate that low doses of a trivalent Trx-L2 vaccine, incorporating L2(20–38) epitopes from HPV16, HPV31 and HPV51, and formulated in a human-compatible adjuvant, induce broadly protective responses. Specifically, we show that this vaccine, which uses a far-divergent archaebacterial thioredoxin as scaffold and is amenable to an easy one-step thermal purification, induces robust cross-neutralization against 12 of the 13 known oncogenic HPV types. Immune performance measured with two different in vitro neutralization assays was corroborated by the results of mouse cervico-vaginal challenge and passive transfer experiments indicating robust cross-protection also in vivo. Altogether, our results attest to the potential of Trx-L2 as a thermostable second-generation HPV vaccine particularly well suited for low-resource countries. Cancer Prev Res; 8(10); 932–41. ©2015 AACR.
Primary Hormonal Therapy for Elderly Breast Cancer Patients: Single Institution Experience
Authors: Panal Mariana , Sánchez-Mendez José I. , Revello Rocio , Abehsera Daniel , de Santiago Javier , Zapardiel Ignacio
Published: July 2015

Aims: Breast cancer is the most frequently diagnosed cancer among women. Up to 50% of breast cancer cases occur in patients over the age of 65 years. Hormonal therapy as a single alternative treatment has been used in this population. The aim of this study was to analyze the oncological outcomes in breast cancer patients who received hormonal therapy alone as a primary treatment. Methods: We retrospectively reviewed our database to find all patients with breast cancer from 2006 to 2011 who were treated with hormonal therapy only at our center. The collected data included patients and tumor characteristics, type of drug administered, follow-up details and type of response obtained using RECIST criteria. Results: We included 44 breast cancer patients. The mean age was 83.5 ± 6.0 years. The majority of patients had tumors with less aggressive immunohistochemical characteristics and 100% of them presented positive estrogen receptors. The pharmacological treatment included exemestane, anastrozole, tamoxifen, letrozole and fulvestrant. The effectiveness rate was 60%, evaluated according to tumor reduction or no progression. Conclusion: The efficacy of hormonal therapy in older patients is reasonably high to justify its use in selected patients. Therefore, it is a sensible alternative for patients who refuse or are unfit for surgery.
Relative Blood Volume Monitoring during Renal Replacement Therapy in Critically Ill Patients with Septic Shock: A Preliminary Report
Authors: Kron Susanne , Leimbach Til , Wenkel Reinhard , Thieme Ulrike , Kern Hartmut , Kron Joachim
Published: July 2015

Background: Volume management during renal replacement therapy (RRT) in septic shock is always in the conflict between aggravating hypovolemia by undue ultrafiltration (UF) and insufficient reduction of fluid overload which is associated with adverse outcome. Relative blood volume (RBV) monitoring could be helpful for timely transition from fluid resuscitation to fluid removal. Methods: Data of RBV were continuously monitored and used for guidance of UF and fluid resuscitation in 21 consecutive patients with severe septic multiple organ failure. RRT was applied with extended daily hemodiafiltration for median 11 h (range 6-23). Changes in RBV were analyzed during the first 4 treatment sessions. Results: During 26 treatments, RBV monitoring revealed an internal volume loss substituted by a median infusion volume of 2.38 l (maximum 8.07 l) per treatment to keep the RBV constant. In the remaining 40 sessions, a median net-UF of 1.00 l (range 0.40-4.40) was achieved. In the first 2 days predominantly substitution was necessary whereas from the third day UF became increasingly possible. The 28-day survival rate was 81%. Conclusion: Blood volume monitoring proved to be an easy and feasible tool for safe guidance of fluid management maintaining the balance between UF and vascular refilling. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=433415.
Declining Estimated Glomerular Filtration Rate and Its Association with Mortality and Comorbidity Over 10 Years in Elderly Women
Authors: Malmgren Linnea , McGuigan Fiona E. , Berglundh Sofia , Westman Kerstin , Christensson Anders , Åkesson Kristina
Published: July 2015

Background/Aims: Renal function deteriorates with age, but a few studies have addressed this longitudinally in elderly women. Our objective was, using 5 estimated glomerular filtration rates (eGFR)-equations, to evaluate changes in renal function and association with adverse outcomes for a decade in 75-year-old women. Methods: Plasma creatinine was measured at ages 75 (n = 1,011), 78 (n = 827), 80 (n = 689) and 85 (n = 363). Glomerular filtration rates were estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease (MDRD); revised Lund-Malmö (LM-rev); Berlin Initiative Study 1 (BIS1) and Cockcroft-Gault/body surface area (CG/BSA) equations. Mortality and comorbidity were investigated in women with chronic kidney disease (CKD) stage 3A and 3B-5. Results: Approximately, 95% of women had eGFR indicating CKD stage 2-3 and progression towards stage 3 was continuous. The women lost 22% of their eGFR during follow-up and loss accelerated between 80 and 85. Mean loss per decade was 16.6 ml/min/1.73 m2. Women in CKD stage 3B-5 had an adjusted hazard ratio for death of 3.5 (95% CI 2.1-5.8) compared to stage 1-2 during follow-up and increased risk of diabetes, heart failure and hypertension. The CG/BSA, BIS1 and LM-rev equations continuously predicted lower eGFR than the MDRD and CKD-EPI equations. Conclusion: eGFR in women aged 75-85 ranges from 30 to 89 ml/min/1.73 m2 (stage 2-3). Decline was 16.6 ml/min/1.73 m2 per decade; accelerated with age and appeared nonlinear. Women with CKD 3B-5 demonstrate an over 3-fold risk of death. eGFR <45 ml/min/1.73 m2 was associated with mortality, confirming the new KDIGO classification 3A and 3B, as clinically applicable in the elderly.
Rare Presentation of Midbrain Infarction: Isolated Medial Rectus Palsy
Authors: Derle Eda , Öcal Ruhsen , Kibaroglu Seda , Can Ufuk
Published: July 2015

A 69-year-old woman presented with sudden onset of diplopia. In neurologic examination left medial rectus palsy without abduction nystagmus was detected. Brain magnetic resonance imaging revealed acute ischemic lesion in mesencephalon on diffusion-weighted images. Sponteneous resolution was observed after 1 month. Medial rectus palsy is a rare presention of acute ischemic stroke and early neuroimaging is important to establish such lesions.
Polycyclic Aromatic Hydrocarbons and Breast Cancer: A Review of the Literature
Authors: Korsh Jessica , Shen Allison , Aliano Kristen , Davenport Thomas
Published: July 2015

Polycyclic aromatic hydrocarbons (PAHs) exist and persist in the atmosphere due to the incomplete combustion of fossil fuels, and are established human carcinogens. The influence of PAHs on the development of breast cancer, the most commonly diagnosed cancer in women worldwide, remains unclear. As established risk factors only account for approximately 41% of the breast cancer cases in the USA, researchers have sought to uncover environmental factors involved in breast cancer development. The breasts are particularly susceptible to aromatic carcinogenesis, and the implementation of biomarkers has provided promising insights regarding PAH-DNA adducts in breast cancer. The use of biomarkers measuring PAH-DNA adducts assesses exposure to eliminate the bias inherent in self-reporting measures in case-control studies investigating the link between PAHs and cancer. Adduct levels reflect exposure dose as well as how the body responds to this exposure, which is partially attributable to genetic variability. Evidence suggests that exposure to PAHs has a causational effect on breast cancer in humans, yet this interaction is not clearly understood. In vitro and animal-based studies have consistently revealed that exposure to PAHs deleteriously affects breast tissue, but there is no definitive link between these compounds and breast cancer.
Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation
Authors: Qin Ling , Tan Yu-rong , Hu Cheng-ping , Liu Xiao-ai , He Ruo-xi
Published: July 2015

Background: Infection of human bronchial epithelial cells (hBECs) with respiratory syncytial virus (RSV) has been shown to induce a Th lymphocyte subset drift, e.g. enhanced differentiation of Th2 and Th17 subsets, which is a classic characteristic of asthma. However, the molecules responsible for the drift in Th subsets remain unknown. This study aims to determine the expression of leptin in RSV-infected hBECs, and its role in Th2 and Th17 cell differentiation and extracellular regulated kinase (ERK) 1/2 phosphorylation. Methods: Cultured hBECs were infected with RSV. mRNA expression of the LEP gene in cells was measured by real-time PCR while LEP protein secretion in culture medium was measured by ELISA. Th differentiation was investigated in cultured human peripheral blood mononuclear cells following stimulation with recombinant human leptin. Th2 and Th17 subsets were examined by flow cytometry. Phosphorylation of the ERK1/2 protein in lymphocytes was detected by Western blot and immunofluorescence. Results: LEP mRNA expression was significantly upregulated in RSV-infected hBECs while the leptin protein level in the supernatants of RSV-infected hBECs was significantly increased. Stimulation of lymphocytes with leptin increased the differentiation of the Th17 subset and ERK1/2 phosphorylation, but suppressed Th2 subset differentiation. Conclusion: Leptin was oversecreted by RSV-infected hBECs, which promoted Th17 subset differentiation but suppressed Th2 subset differentiation possibly via regulating ERK1/2 phosphorylation.
Genetic Deficiency of Glutathione
S
-Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury
Authors: Conklin Daniel J. , Guo Yiru , Jagatheesan Ganapathy , Kilfoil Peter J. , Haberzettl Petra , Hill Bradford G. , Baba Shahid P. , Guo Luping , Wetzelberger Karin , Obal Detlef , Rokosh D. Gregg , Prough Russell A. , Prabhu Sumanth D. , Velayutham Murugesan , Zweier Jay L. , Hoetker J. David , Riggs Daniel W. , Srivastava Sanjay , Bolli Roberto , Bhatnagar Aruni
Published: July 2015

Rationale:

Myocardial ischemia–reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation–derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed.

Objective:

We tested the hypothesis that removal of aldehydes by glutathione
S
-transferase P (GSTP) diminishes I/R injury.

Methods and Results:

In adult male C57BL/6 mouse hearts,
Gstp1/2
was the most abundant GST transcript followed by
Gsta4
and
Gstm4.1
, and GSTP activity was a significant fraction of the total GST activity.
mGstp1/2
deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism of 4-hydroxy-
trans
-2-nonenal or
trans
-2-hexanal; on ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than wild-type hearts. GSTP deficiency did not affect I/R-induced free radical generation, c-Jun N-terminal kinase activation, or depletion of reduced glutathione. Acrolein exposure induced a hyperpolarizing shift in
I
Na
, and acrolein-induced cell death was delayed by SN-6, a Na
+
/Ca
++
exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than wild-type myocytes to acrolein-induced protein crosslinking and cell death.

Conclusions:

GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes, such as acrolein.
Caval Penetration by Inferior Vena Cava Filters
Authors: Jia Zhongzhi , Wu Alex , Tam Mathew , Spain James , McKinney J. Mark , Wang Weiping
Published: July 2015

Background—

Limited penetration into the caval wall is an important securing mechanism for inferior vena cava (IVC) filters; however, caval penetration can also cause unintentional complications. The aim of this study was to assess the incidence, severity, clinical consequences, and management of filter penetration across a range of commercially available IVC filters.

Methods and Results—

The MEDLINE database was searched for all studies (1970–2014) related to IVC filters. A total of 88 clinical studies and 112 case reports qualified for analysis; these studies included 9002 patients and 15 types of IVC filters. Overall, penetration was reported in 19% of patients (1699 of 9002), and 19% of those penetrations (322 of 1699) showed evidence of organ/structure involvement. Among patients with penetration, 8% were symptomatic, 45% were asymptomatic, and 47% had unknown symptomatology. The most frequently reported symptom was pain (77%, 108 of 140). Major complications were reported in 83 patients (5%). These complications required interventions including surgical removal of the IVC filter (n=63), endovascular stent placement or embolization (n=11), endovascular retrieval of the permanent filter (n=4), and percutaneous nephrostomy or ureteral stent placement (n=3). Complications led to death in 2 patients. A total of 87% of patients (127 of 146) underwent premature filter retrieval or interventions for underlying symptoms or penetration-related complications.

Conclusions—

Caval penetration is a frequent but clinically underrecognized complication of IVC filter placement. Symptomatic patients accounted for nearly 1/10th of all penetrations; most of these cases had organ/structure involvement. Interventions with endovascular retrieval and surgery were required in most of these symptomatic patients.
Critical Role of Striatin in Blood Pressure and Vascular Responses to Dietary Sodium Intake
Authors: Garza Amanda E. , Pojoga Luminita H. , Moize Burhanuddin , Hafiz Wan M. , Opsasnick Lauren A. , Siddiqui Waleed T. , Horenstein Michael , Adler Gail K. , Williams Gordon H. , Khalil Raouf A.
Published: July 2015

Striatin is a protein regulator of vesicular trafficking in neurons that also binds caveolin-1 and Ca
2+
-calmodulin and could activate endothelial nitric oxide synthase. We have shown that striatin colocalizes with the mineralocorticoid receptor and that mineralocorticoid receptor activation increases striatin levels in vascular cells. To test whether striatin is a regulator of vascular function, wild-type and heterozygous striatin-deficient mice (Strn
+/−
) were randomized in crossover intervention to restricted (0.03%) and liberal sodium (1.6%) diets for 7 days on each diet, and blood pressure and aortic vascular function were measured. Compared with wild-type, sodium restriction significantly reduced blood pressure in Strn
+/−
. On liberal salt intake, phenylephrine and high KCl caused a greater vascular contraction in Strn
+/−
than wild-type, and endothelium removal, nitric oxide synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ enhanced phenylephrine contraction to a smaller extent in Strn
+/−
than wild-type. On liberal salt, acetylcholine relaxation was less in Strn
+/−
than in wild-type, and endothelium removal, L-NAME, and ODQ blocked acetylcholine relaxation, suggesting changes in endothelial NO-cGMP. On liberal salt, endothelial nitric oxide synthase mRNA expression and the ratio of endothelial nitric oxide synthase activator pAkt/total Akt were decreased in Strn
+/−
versus wild-type. Vascular relaxation to NO donor sodium nitroprusside was not different among groups. Thus, striatin deficiency is associated with salt sensitivity of blood pressure, enhanced vasoconstriction, and decreased vascular relaxation, suggesting a critical role for striatin, through modulation of endothelial NO-cGMP, in regulation of vascular function and BP during changes in sodium intake.
Ethnic Differences in Associations Between Blood Pressure and Stroke in South Asian and European Men
Authors: Eastwood Sophie V. , Tillin Therese , Chaturvedi Nish , Hughes Alun D.
Published: July 2015

It is unknown whether associations between blood pressure (BP) and stroke vary between Europeans and South Asians, despite higher stroke rates in the latter. We report findings from a UK cohort study of 1375 European and 1074 South Asian men, not receiving antihypertensive medication, aged 40 to 69 years at baseline (1988–1991). Assessment included BP, blood tests, anthropometry, and questionnaires. Incident stroke was established at 20 years from death certification, hospital and primary care records, and participant report. South Asians had higher systolic BP, diastolic BP, and mean arterial pressure than Europeans, and similar pulse pressure. Associations between systolic BP or diastolic BP and stroke were stronger in South Asians than Europeans, after adjustment for age, smoking status, waist/hip ratio, total/high-density lipoprotein-cholesterol ratio, diabetes mellitus, fasting glucose, physical activity, and heart rate (systolic BP: Europeans [odds ratio, 1.22; 95% confidence interval, 0.98–1.51], South Asians [1.56; 1.24–1.95]; ethnic difference
P
=0.04; diastolic BP: Europeans [0.90; 0.71–1.13], South Asians [1.68; 1.32–2.15];
P
<0.001). Hemodynamic correlates of stroke risk differed by ethnicity: in combined models, mean arterial pressure but not pulse pressure was detrimentally associated with stroke in South Asians, whereas the converse was true for Europeans. The combination of hyperglycemia and hypertension appeared particularly detrimental for South Asians. There are marked ethnic differences in associations between BP parameters and stroke. Undue focus on systolic BP for risk prediction, and current age and treatment thresholds may be inappropriate for individuals of South Asian ancestry.
Healthcare Costs Attributable to Hypertension
Authors: Weaver Colin G. , Clement Fiona M. , Campbell Norm R.C. , James Matthew T. , Klarenbach Scott W. , Hemmelgarn Brenda R. , Tonelli Marcello , McBrien Kerry A.
Published: July 2015

Accurately documenting the current and future costs of hypertension is required to fully understand the potential economic impact of currently available and future interventions to prevent and treat hypertension. The objective of this work was to calculate the healthcare costs attributable to hypertension in Canada and to project these costs to 2020. Using population-based administrative data for the province of Alberta, Canada (>3 million residents) from 2002 to 2010, we identified individuals with and without diagnosed hypertension. We calculated their total healthcare costs and estimated costs attributable to hypertension using a regression model adjusting for comorbidities and sociodemographic factors. We then extrapolated hypertension-attributable costs to the rest of Canada and projected costs to the year 2020. Twenty-one percent of adults in Alberta had diagnosed hypertension in 2010, with a projected increase to 27% by 2020. The average individual with hypertension had annual healthcare costs of $5768, of which $2341 (41%) were attributed to hypertension. In Alberta, the healthcare costs attributable to hypertension were $1.4 billion in 2010. In Canada, the hypertension-attributable costs were estimated to be $13.9 billion in 2010, rising to $20.5 billion by 2020. The increase was ascribed to demographic changes (52%), increasing prevalence (16%), and increasing per-patient costs (32%). Hypertension accounts for a significant proportion of healthcare spending (10.2% of the Canadian healthcare budget) and is projected to rise even further. Interventions to prevent and treat hypertension may play a role in limiting this cost growth.