bluuebunny/crossref_metadata_2025 huggingface dataset:
The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure
Authors: Schepelmann M. , Yarova P. L. , Lopez-Fernandez I. , Davies T. S. , Brennan S. C. , Edwards P. J. , Aggarwal A. , Graça J. , Rietdorf K. , Matchkov V. , Fenton R. A. , Chang W. , Krssak M. , Stewart A. , Broadley K. J. , Ward D. T. , Price S. A. , Edwards D. H. , Kemp P. J. , Riccardi D.
Published: November 2015

The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative [wild-type (WT)] and Cre-positive SM22αCaSRΔflox/Δflox [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca2+) concentrations (1–5 mM) evoked contraction in WT but only relaxation in KO aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either nitric oxide-synthase inhibition with nitro-l-arginine methyl ester or by a high-salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia, and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca2+ concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.
Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways
Authors: Mapanga Rudo F. , Essop M. Faadiel
Published: October 2015

The incidence of cardiovascular complications associated with hyperglycemia is a growing global health problem. This review discusses the link between hyperglycemia and cardiovascular diseases onset, focusing on the role of recently emerging downstream mediators, namely, oxidative stress and glucose metabolic pathway perturbations. The role of hyperglycemia-mediated activation of nonoxidative glucose pathways (NOGPs) [i.e., the polyol pathway, hexosamine biosynthetic pathway, advanced glycation end products (AGEs), and protein kinase C] in this process is extensively reviewed. The proposal is made that there is a unique interplay between NOGPs and a downstream convergence of detrimental effects that especially affect cardiac endothelial cells, thereby contributing to contractile dysfunction. In this process the AGE pathway emerges as a crucial mediator of hyperglycemia-mediated detrimental effects. In addition, a vicious metabolic cycle is established whereby hyperglycemia-induced NOGPs further fuel their own activation by generating even more oxidative stress, thereby exacerbating damaging effects on cardiac function. Thus NOGP inhibition, and particularly that of the AGE pathway, emerges as a novel therapeutic intervention for the treatment of cardiovascular complications such as acute myocardial infarction in the presence hyperglycemia.
Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits
Authors: Schiller Alicia M. , Pellegrino Peter R. , Zucker Irving H.
Published: November 2015

Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self-affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits.
Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice
Authors: Leibrock Christina B. , Voelkl Jakob , Kohlhofer Ursula , Quintanilla-Martinez Leticia , Kuro-o Makoto , Lang Florian
Published: November 2015

Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic ( kl/kl) mice, excessive 1,25(OH)2D3formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3did not significantly affect plasma concentrations of 1,25(OH)2D3and Ca2+but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice.
Mesenchymal stem cells and chronic renal artery stenosis
Authors: Oliveira-Sales Elizabeth B. , Boim Mirian A.
Published: November 2015

Renal artery stenosis is the main cause of renovascular hypertension and results in ischemic nephropathy characterized by inflammation, oxidative stress, microvascular loss, and fibrosis with consequent functional failure. Considering the limited number of strategies that effectively control renovascular hypertension and restore renal function, we propose that cell therapy may be a promising option based on the regenerative and immunosuppressive properties of stem cells. This review addresses the effects of mesenchymal stem cells (MSC) in an experimental animal model of renovascular hypertension known as 2 kidney-1 clip (2K-1C). Significant benefits of MSC treatment have been observed on blood pressure and renal structure of the stenotic kidney. The mechanisms involved are discussed.
Experimental evidence of age-related adaptive changes in human acinar airways
Authors: Quirk James D. , Sukstanskii Alexander L. , Woods Jason C. , Lutey Barbara A. , Conradi Mark S. , Gierada David S. , Yusen Roger D. , Castro Mario , Yablonskiy Dmitriy A.
Published: November 2015

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized 3He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized 3He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger.
Changes in cortical activity measured with EEG during a high-intensity cycling exercise
Authors: Enders Hendrik , Cortese Filomeno , Maurer Christian , Baltich Jennifer , Protzner Andrea B. , Nigg Benno M.
Published: November 2015

This study investigated the effects of a high-intensity cycling exercise on changes in spectral and temporal aspects of electroencephalography (EEG) measured from 10 experienced cyclists. Cyclists performed a maximum aerobic power test on the first testing day followed by a time-to-exhaustion trial at 85% of their maximum power output on 2 subsequent days that were separated by ∼48 h. EEG was recorded using a 64-channel system at 500 Hz. Independent component (IC) analysis parsed the EEG scalp data into maximal ICs. An equivalent current dipole model was calculated for each IC, and results were clustered across subjects. A time-frequency analysis of the identified electrocortical clusters was performed to investigate the magnitude and timing of event-related spectral perturbations. Significant changes ( P < 0.05) in electrocortical activity were found in frontal, supplementary motor and parietal areas of the cortex. Overall, there was a significant increase in EEG power as fatigue developed throughout the exercise. The strongest increase was found in the frontal area of the cortex. The timing of event-related desynchronization within the supplementary motor area corresponds with the onset of force production and the transition from flexion to extension in the pedaling cycle. The results indicate an involvement of the cerebral cortex during the pedaling task that most likely involves executive control function, as well as motor planning and execution.
Inverse Problem of Air Filtration of Nanoparticles: Optimal Quality Factors of Fibrous Filters
Authors: Shou Dahua , Fan Jintu , Ye Lin , Zhang Heng , Qian Xiaoming , Zhang Zhong
Published: November 2015

Application of nanofibers has become an emerging approach to enhance filtration efficiency, but questions arise about the decrease in Quality factor (QF) for certain particles due to the rapidly increasing pressure drop. In this paper, we theoretically investigate the QF of dual‐layer filters for filtration of monodisperse and polydisperse nanoparticles. The inverse problem of air filtration, as defined in this work, consists in determining the optimal construction of the two‐layer fibrous filter with the maximum QF. In comparison to a single‐layer substrate, improved QF values for dual‐layer filters are found when a second layer with proper structural parameters is added. The influences of solidity, fiber diameter, filter thickness, face velocity, and particle size on the optimization of QF are studied. The maximum QF values for realistic polydisperse particles with a lognormal size distribution are also found. Furthermore, we propose a modified QF (MQF) accounting for the effects of energy cost and flow velocity, which are significant in certain operations. The optimal MQF of the dual‐layer filter is found to be over twice that of the first layer. This work provides a quick tool for designing and optimizing fibrous structures with better performance for the air filtration of specific nanoparticles.
Quantitative Shotgun Proteomics Analysis of Rice Anther Proteins after Exposure to High Temperature
Authors: Kim Mijeong , Kim Hijin , Lee Wondo , Lee Yoonjung , Kwon Soon-Wook , Lee Joohyun
Published: November 2015

In rice, the stage of development most sensitive to high temperature stress is flowering, and exposure at this stage can result in spikelet sterility, thereby leading to significant yield losses. In this study, protein expression patterns of rice anthers from Dianxi4, a high temperature tolerant Japonica rice variety, were compared between samples exposed to high temperature and those grown in natural field conditions in Korea. Shotgun proteomics analysis of three replicate control and high-temperature-treated samples identified 3,266 nonredundant rice anther proteins (false discovery rate < 0.01). We found that high levels of ATP synthase, cupin domain-containing proteins, and pollen allergen proteins were present in rice anthers. Comparative analyses of 1,944 reproducibly expressed proteins identified 139 differentially expressed proteins, with 95 increased and 44 decreased in response to high temperature conditions. Heat shock, DnaK family, and chaperone proteins showed highly increased expression, suggesting that the high temperature tolerance of Dianxi4 is achieved by stabilization of proteins in pollen cells. Trehalose synthase was also highly increased after heat treatment, suggesting a possible role for trehalose in preventing protein denaturation through desiccation.
Effect of Indole-3-Butyric Acid on Clonal Propagation of Swietenia macrophylla through Branch Cutting
Authors: Azad Md. Salim , Matin Md. Abdul
Published: November 2015

The study discloses the scopes of clonal propagation Swietenia macrophylla through branch cutting treated with IBA. A total of four hundred cuttings were used with four replications to assess the rooting ability. The study exposed significant (p<0.5) difference of rooted cuttings among the treatments. The highest (62.51%) rooting percent was observed in cutting with 0.4% IBA treatment. In addition, root number and its length per cutting were increased with increasing IBA concentration (p<0.5). The experiment showed significant (p<0.5) difference of sprouting among the treatments. The highest (67.27%) percent of sprouting was observed in cuttings with 0.4% solution, which showed a similar fashion of percent of rooting. The study also showed significant (p<0.5) difference of shoot number per cutting, the length of the longest shoot, and number of leaves per cutting among the treatments. The overall survival of rooted cuttings after transfer to polybag significantly (p<0.5) differed among the cuttings treated with different IBA solution. The highest survival percentage (69.67%) was observed in the cuttings rooted with 0.4% IBA treatment and the lowest (55.6%) survival was found in cuttings treated with control. The use of 0.4% IBA treatment is suggested for rooting of juvenile leafy branch cutting of S. macrophylla.
Maresin 1 Inhibits TRPV1 in Temporomandibular Joint‐Related Trigeminal Nociceptive Neurons and TMJ Inflammation‐Induced Synaptic Plasticity in the Trigeminal Nucleus
Authors: Park Chul-Kyu
Published: November 2015

In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ). Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage‐derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1) in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye), I showed that maresin 1 potently inhibits capsaicin‐induced TRPV1 currents and neuronal activity via Gαi‐coupled G‐protein coupled receptors in DiI‐labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist‐evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation‐induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ‐inflammatory pain in the orofacial region.
Variations in Antioxidant Genes and Male Infertility
Authors: Yu Bolan , Huang Zhaofeng
Published: November 2015

Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathioneS-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.
Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?
Authors: Xue Chunyan , Rosen Richard , Jordan Adrienne , Hu Dan-Ning
Published: November 2015

Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons) against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases.
Fear of Falling in Women with Fibromyalgia and Its Relation with Number of Falls and Balance Performance
Authors: Collado-Mateo D. , Gallego-Diaz J. M. , Adsuar J. C. , Domínguez-Muñoz F. J. , Olivares P. R. , Gusi N.
Published: November 2015

Objective. To evaluate fear of falling, number of falls, and balance performance in women with FM and to examine the relationship between these variables and others, such as balance performance, quality of life, age, pain, and impact of fibromyalgia.Methods. A total of 240 women participated in this cross-sectional study. Of these, 125 had fibromyalgia. Several variables were assessed: age, fear of falling from 0 to 100, number of falls, body composition, balance performance, lower limb strength, health-related quality of life, and impact of fibromyalgia.Results. Women with fibromyalgia reported more falls and more fear of falling. Fear of falling was associated with number of falls in the last year, stiffness, perceived balance problems, impact of FM, and HRQoL whereas the number of falls was related to fear of falling, balance performance with eyes closed, pain, tenderness to touch level, anxiety, self-reported balance problems, impact of FM, and HRQoL.Conclusion. FM has an impact on fear of falling, balance performance, and number of falls. Perceived balance problems seem to be more closely associated with fear of falling than objective balance performance.
Effect of Processing on Mechanically Alloyed and Spark Plasma Sintered Al‐Al2O3 Nanocomposites
Authors: Saheb Nouari , Shahzeb Khan Muhammad , Hakeem Abbas Saeed
Published: November 2015

Metal matrix nanocomposites are advanced materials developed using ceramic nanoreinforcements and nanocrystalline metal matrices. These composites have outstanding properties and high potential for large number of functional and structural applications. In this work, nanocrystalline aluminium and Al‐Al2O3 nanocomposites were synthesised using mechanical alloying and consolidated through spark plasma sintering technique. Scanning electron microscopy, X‐ray diffraction, and mapping were used to characterize the powders and sintered samples. Density and hardness of sintered samples were measured using densimeter and hardness tester, respectively. It was found that milling of pure aluminium for 24 h reduced its crystallite size to less than 100 nm. For Al‐Al2O3 nanocomposites, milling for 24 h decreased the crystallite size of the aluminium phase and resulted in uniform dispersion of the reinforcement. Sintering of the synthesised powders led to grain growth. Al2O3 contributed to growth inhibition when samples were sintered for 20 minutes and improved the hardness but reduced densification. The Al‐10 vol.%  Al2O3 nanocomposite had the highest Vickers hardness value of 1460 MPa.
HPV Infection, but Not EBV or HHV-8 Infection, Is Associated with Salivary Gland Tumours
Authors: Hühns Maja , Simm Georg , Erbersdobler Andreas , Zimpfer Annette
Published: November 2015

Benign and malignant salivary gland tumours are clinically heterogeneous and show different histology. Little is known about the role of human herpes virus 8 (HHV-8), Epstein-Barr virus (EBV), and human papillomavirus (HPV) infection in salivary gland neoplasms. We investigated the presence of the three viruses in formalin-fixed, paraffin-embedded tissue samples in a cohort of 200 different salivary gland tumours. We performed EBV-LMP-1 and HHV-8 and p16 immunohistochemistry, a specific chip based hybridization assay for detection and typing of HPV and a chromogenic in situ hybridization for EBV analysis. Only one case, a polymorphic low-grade carcinoma, showed HHV-8 expression and one lymphoepithelial carcinoma was infected by EBV. In 17 cases (9%) moderate or strong nuclear and cytoplasmic p16 expression was detected. The HPV type was investigated in all of these cases and additionally in 8 Warthin’s tumours. In 19 cases HPV type 16 was detected, mostly in Warthin’s tumour, adenoid cystic carcinoma, and adenocarcinoma NOS. We concluded that HHV-8 infection and EBV infection are not associated with salivary gland cancer, but HPV infection may play a role in these tumour entities.
Optimization ofArundo donaxSaccharification by (Hemi)cellulolytic Enzymes fromPleurotus ostreatus
Authors: Liguori Rossana , Ionata Elena , Marcolongo Loredana , Vandenberghe Luciana Porto de Souza , La Cara Francesco , Faraco Vincenza
Published: November 2015

An enzymatic mixture of cellulases and xylanases was produced byPleurotus ostreatususing microcrystalline cellulose as inducer, partially characterized and tested in the statistical analysis ofArundo donaxbioconversion. The Plackett-Burman screening design was applied to identify the most significant parameters for the enzymatic hydrolysis of pretreatedA. donax. As the most significant influence during the enzymatic hydrolysis ofA. donaxwas exercised by the temperature (°C), pH, and time, the combined effect of these factors in the bioconversion byP. ostreatuscellulase and xylanase was analyzed by a 33factorial experimental design. It is worth noting that the best result of 480.10 mg of sugars/gds, obtained at 45°C, pH 3.5, and 96 hours of incubation, was significant also when compared with the results previously reached by process optimization with commercial enzymes.
Variations in the Intragene Methylation Profiles Hallmark Induced Pluripotency
Authors: Druzhkov Pavel , Zolotykh Nikolay , Meyerov Iosif , Alsaedi Ahmed , Shutova Maria , Ivanchenko Mikhail , Zaikin Alexey
Published: November 2015

We demonstrate the potential of differentiating embryonic and induced pluripotent stem cells by the regularized linear and decision tree machine learning classification algorithms, based on a number of intragene methylation measures. The resulting average accuracy of classification has been proven to be above 95%, which overcomes the earlier achievements. We propose a constructive and transparent method of feature selection based on classifier accuracy. Enrichment analysis reveals statistically meaningful presence of stemness group and cancer discriminating genes among the selected best classifying features. These findings stimulate the further research on the functional consequences of these differences in methylation patterns. The presented approach can be broadly used to discriminate the cells of different phenotype or in different state by their methylation profiles, identify groups of genes constituting multifeature classifiers, and assess enrichment of these groups by the sets of genes with a functionality of interest.
La Educación en Negocios: Una Discusión Siempre Relevante
Authors: Mandiola Marcela
Published: November 2015

La contingencia social en nuestro país ha relevado la necesidad de problematizar la práctica de la educación en negocios que ofrecen nuestras instituciones de educación superior. Pero más allá de cuestionar particulares programas o instituciones, lo que estaría en discusión son sus supuestos y propósitos. A través de la distinción entre práctica y campo de estudios en educación en negocios, este artículo aspira a contribuir con una voz crítica a dicha discusión.
Sporadic Case of Breast Angiosarcoma as a Complication of Radiotherapy Following Breast-Conserving Surgery for Invasive Ductal Breast Cancer
Authors: Grebić Damir , Tomašić Ana Marija
Published: November 2015

Background: Angiosarcomas are highly aggressive and malignant blood vessel tumors. Rarely, angiosarcomas develop in the breast following conservative therapy, namely radiotherapy. Case Report: A 70-year-old female patient presented with dark purple discoloration of the skin of the right breast. 6 years earlier, the patient had undergone conservative surgery for invasive ductal carcinoma of the right breast. According to the breast-conserving surgery protocol, the patient had been treated with radiotherapy to the residual breast tissue. The patient's annual mammograms and ultrasound findings were normal. The skin lesion was superficially localized mostly at the border between the upper and lower medial quadrants of the breast (between 2 and 4 o'clock) and above the areola. The borders were uneven; the dimensions were 7 cm × 4 cm. The mammogram was classified as Breast Imaging Report and Data System (BI-RADS) 2. Ultrasound examination showed a well-vascularized structure, although the etiology was unclear. A tissue biopsy revealed angiosarcoma. The patient underwent radical simplex mastectomy. Following surgery, the patient underwent chemotherapy. Tests excluded metastases for a follow-up period of 5 years. Conclusion: Angiosarcomas that develop after radiotherapy following breast-conserving surgery are sporadic, but it is important to take this possible incident into consideration during treatment.
Lidocaine Skin Patch (Lidopat® 5%) Is Effective in the Treatment of Traumatic Rib Fractures: A Prospective Double-Blinded and Vehicle-Controlled Study
Authors: Cheng Yu-Jen
Published: November 2015

Objective: The purpose of this study was to determine the efficacy of the Lidopat® 5% skin patch in relieving rib fracture pain. Subjects and Methods: From June 2009 to May 2011, 44 trauma patients with isolated rib fractures were enrolled in this study and randomized in a double-blind method into 2 groups. The experimental group (group E: 27 patients) used a Lidopat® 5% skin patch at the trauma site and took an oral analgesic drug for pain relief. The placebo group (group P: 17 patients) used a placebo vehicle patch and an oral analgesic drug. Results: The mean age, weight and hospital stay of patients were 56.8 ± 13.8 years, 67.4 ± 12.6 kg and 6.34 ± 1.3 days, respectively. In the first 4 days, there were no significant differences in pain scores between the groups (p > 0.05). After the 5th day, the average pain score was significantly less in group E (mean 1.5) than in group P (mean 3.10; p < 0.05). There was no significant difference in the number of fractured ribs between groups (p = 0.904). The use of meperidine and the length of hospital stay (6.0 vs. 6.9 days) were both significantly less in group E (p = 0.043 and 0.009, respectively). Conclusion: In this study, the use of the Lidopat® 5% skin patch in patients with isolated rib fractures alleviated pain and shortened the hospital stay, and a lower dose of pain-relieving medication was used.
Degree of Rectal Distension Seen on Prostate Radiotherapy Planning CT Scan Is Not a Negative Prognostic Factor in the Modern Era of Image-Guided Radiotherapy
Authors: Silverman Rafael , Johnson Kerstie , Perry Christina , Sundar Santhanam
Published: November 2015

Background: Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk. We tested whether imaging during radiotherapy helps minimise the negative impact that rectal distension has on long-term tumour control. Findings: The rectal diameter (anterior/posterior and lateral) was prospectively measured at radiotherapy planning in 172 consecutive patients undergoing radical radiotherapy with three-dimensional conformal radiotherapy. Daily, and then weekly, imaging during radiotherapy ensured that prostate movement remained within predefined tolerances. Patients were followed up for a median of 72 months with regular prostate-specific antigen (PSA) measurements to ascertain biochemical PSA relapse and survival information. Conclusions: In this cohort of predominately high-risk localised prostate cancer, rectal distension had no significant impact on PSA relapse. We suggest that regular imaging during radiotherapy negates the risk caused by rectal distension on local treatment failure.
Fluctuations in Pigment Epithelial Detachment and Retinal Fluid Using a Bimonthly Treatment Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration
Authors: Zinkernagel Martin Sebastian , Wolf Sebastian , Ebneter Andreas
Published: November 2015

Purpose: To assess the effect of a bimonthly treatment regimen with intravitreal aflibercept on retinal fluid and pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (AMD). Methods: Twenty-six treatment-naive eyes of 26 patients with choroidal neovascularisation secondary to AMD were included. The patients received three initial monthly (mean 30 days) intravitreal injections of aflibercept followed by a bimonthly (mean 62 days) fixed regimen for a total of 1 year. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were recorded at monthly intervals. In addition, the presence of intraretinal fluid (IRF) or subretinal fluid (SRF) or a combination of both as well as serous and fibrovascular PEDs were assessed. Results: The mean patient age was 80 years (range 54-93). There were 14 male and 12 female patients. The mean gain in BCVA at 1 year was 9.3 letters (SEM ±3) with a mean reduction of the central retinal thickness of 154 µm (SEM ±50). After 3 monthly injections of aflibercept, there was resolution of IRF and SRF in 80% of the treated eyes; the amount of fluid increased at months 4, 6 and 8 with troughs in between. Whereas fibrovascular PEDs remained stable after the loading phase, serous PEDs displayed a seesaw pattern. Patients without retinal pigment epithelium (RPE) atrophy at the end of the 1-year period had significantly better BCVA compared to patients with RPE atrophy (p = 0.03). Conclusion: Despite significant overall BCVA gain, bimonthly intervals seem insufficient to maintain the morphological improvements after the initial loading dose with intravitreal aflibercept.
Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis
Authors: Creemers Esther E. , van Rooij Eva
Published: November 2015

Cardiac fibrosis as a result of excessive extracellular matrix deposition leads to stiffening of the heart, which can eventually lead to heart failure. An important event in cardiac fibrosis is the transformation of fibroblasts into myofibroblasts, which secrete large amounts of extracellular matrix proteins. Although the function of protein-coding genes in myofibroblast activation and fibrosis have been a topic of investigation for a long time, it has become clear that noncoding RNAs also play key roles in cardiac fibrosis. This review discusses the involvement of microRNAs and long noncoding RNAs in cardiac fibrosis and summarizes the issues related to translating these findings into real-life therapies.
Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia
Authors: Gerstein Hertzel C. , Paré Guillaume , McQueen Matthew J. , Haenel Heinz , Lee Shun Fu , Pogue Janice , Maggioni Aldo P. , Yusuf Salim , Hess Sibylle
Published: October 2015

Background—

Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Biobanked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction With Initial Glargine Intervention trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcome or death when added to clinical measurements.

Methods and Results—

A multiplex analysis measured a panel of cardiometabolic biomarkers in 1 mL of stored frozen serum from every participant who provided biobanked blood. After eliminating undetectable or unanalyzable biomarkers, 8401 participants who each had a set of 237 biomarkers were analyzed. Forward-selection Cox regression models were used to identify biomarkers that were each independent determinants of 3 different incident outcomes: (1) the composite of myocardial infarction, stroke, or CV death; (2) these plus heart failure hospitalization or revascularization; and (3) all-cause death. When added to clinical variables, 10 biomarkers were independent determinants of the 1405 CV composite outcomes observed during follow-up; 9 biomarkers (including 8 of these 10) were independent determinants of the 2435 expanded composite outcomes; and 15 (including the 10 CV composite biomarkers) were independent determinants of the 1340 deaths. Adjusted C statistics increased from 0.64 for the clinical variables to 0.71 and 0.68 for the 2 CV composite outcomes, respectively, with the greatest increase to 0.75 for death (
P
<0.001 for the change).

Conclusions—

A systematic hypothesis-free approach identified combinations of up to 15 cardiometabolic biomarkers as independent determinants of CV outcomes or death in people with dysglycemia.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00069784.
Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood–Brain Barrier Integrity and Central Nervous System Homeostasis
Authors: Tran Khiem A. , Zhang Xianming , Predescu Dan , Huang Xiaojia , Machado Roberto F. , Göthert Joachim R. , Malik Asrar B. , Valyi-Nagy Tibor , Zhao You-Yang
Published: November 2015

Background—

The blood–brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB.

Methods and Results—

Using a mouse model with tamoxifen-inducible endothelial cell–restricted disruption of
ctnnb1
(
iCKO
), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The
iCKO
mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients.

Conclusions—

These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation.
Study of Cardiovascular Health Outcomes in the Era of Claims Data
Authors: Psaty Bruce M. , Delaney Joseph A. , Arnold Alice M. , Curtis Lesley H. , Fitzpatrick Annette L. , Heckbert Susan R. , McKnight Barbara , Ives Diane , Gottdiener John S. , Kuller Lewis H. , Longstreth W.T.
Published: November 2015

Background—

Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes.

Methods and Results—

Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected
International Classification of Diseases, Ninth Edition
diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare & Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of
International Classification of Diseases, Ninth Edition
code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI.

Conclusions—

The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations.
Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures in Patients With Congenital Heart Disease
Authors: Beauséjour Ladouceur Virginie , Lawler Patrick R. , Gurvitz Michelle , Pilote Louise , Eisenberg Mark J. , Ionescu-Ittu Raluca , Guo Liming , Marelli Ariane J.
Published: November 2015

Background—

The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD.

Methods and Results—

In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year (
P
<0.0001). This increase was attributable to increases in rates per 1000 CHD patients in diagnostic cardiac catheterizations (11.7 to 13.7 per 1000), structural heart interventions (1.0 to 5.2 per 1000), coronary interventions (1.0 to 2.4 per 1000), pacemaker/implantable cardioverter-defibrillator insertions (1.6 to 4.4 per 1000), nuclear procedures (4.2 to 13.8 per 1000), and computed tomography scans of the chest (2.5 to 12.3 per 1000). Over time, among children with CHD, the median age at first LDIR procedure decreased from 5.0 years to 9.6 months. Severity of CHD significantly predicted extent of exposure.

Conclusions—

From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.
Crisis and Interest
Authors: Parrilla Ricard , Almiron Núria , Xifra Jordi
Published: October 2015

This article analyzes the inputs and constituencies (funding, founders, trustees, and experts) of the most influential group of think tanks in Spain during the great recession (2008-2015) in order to assess how far these think tanks were connected to other interest groups providing support for neoliberal policies. The aim of the article is to advance knowledge on think tank theory and it addresses three research goals: (a) assessing how far Spanish think tanks are affected by political clientelism and financialization, (b) identifying those actors who direct Spanish think tanks and collaborate with them, and (c) assessing the think tanks’ connections with international lobbying networks. Our results show that the think tanks studied are consistently related to three types of actor—political, economic, and academic—while also maintaining strong ties with the media. In this regard, their main traits are a pluralism biased toward right and center-left stances, state and party clientelism, the financial and political instrumentalization of party tanks, and the superior ability of conservative tanks to build network coalitions.
Bullying on Television
Authors: Petranovich Kaitlin A. , Bapty Samantha J. , Maestas Travis S. , Strasburger Victor C.
Published: November 2015

Bullying is a serious issue for adolescents, with health consequences both at the time of victimization and later on in adulthood. Aggression in the media is an area that has been explored as a contributing factor to bullying behavior. This study aims to determine if the incidence of aggression in popular television shows over the past 50 years has changed. A total of 198 episodes of the most popular television shows between the years 1960 and 2010 were coded for incidents of aggression and analyzed using simple linear regression. The mean number of events per episode was 8.8. No statistically significant correlation was found between number of bullying events and the years in which they occurred. Whereas it is possible that aggression on television may have an impact on bullying behaviors, there is no evidence that the incidence of bullying on television has changed significantly in the past 5 decades.
Sexual Health Knowledge and Needs
Authors: Meldrum Rebecca M. , Liamputtong Pranee , Wollersheim Dennis
Published: November 2015

In this article, we discuss the sexual health knowledge and needs among young Muslim women living in Melbourne, Australia. Eleven young Muslim women were individually interviewed about issues relating to sexual health knowledge and needs, access to sexual health services, and their experiences of balancing their lives in relation to sexual health. Findings revealed a marked influence of religion and culture on sexual health of young Muslim women. They often faced challenges balancing Muslim culture, Australian culture, and Islamic religion. Our findings have implications for health services in a multicultural society. They could be used to promote culturally sensitive sexual health services for young Muslim women in Australia and elsewhere.
Support for National Health Insurance Seven Years Into Massachusetts Healthcare Reform
Authors: Saluja Sonali , Zallman Leah , Nardin Rachel , Bor David , Woolhandler Steffie , Himmelstein David U. , McCormick Danny
Published: November 2015

Before the Affordable Care Act (ACA), many surveys showed majority support for national health insurance (NHI), also known as single payer; however, little is currently known about views of the ACA's targeted population. Massachusetts residents have had seven years of experience with state health care reform that became the model for the ACA. We surveyed 1,151 adults visiting safety-net emergency departments in Massachusetts in late 2013 on their preference for NHI or the Massachusetts reform and on their experiences with insurance. Most of the patients surveyed were low-income and non-white. The majority of patients (72.0%) preferred NHI to the Massachusetts reform. Support for NHI among those with public insurance, commercial insurance, and no insurance was 68.9%, 70.3%, and 86.3%, respectively ( p < .001). Support for NHI was higher among patients dissatisfied with their insurance plan (83.3% vs. 68.9%, p = .014), who delayed medical care (81.2% vs. 69.6%, p < .001) or avoided purchasing medications due to cost (87.3% vs. 71.4%; p = .01). Majority support for NHI was observed in every demographic subgroup. Given the strong support for NHI among disadvantaged Massachusetts patients seven years after state health reform, a reappraisal of the ACA's ability to meet the needs of underserved patients is warranted.