bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction suppression in monkey inferotemporal cortex depends on the conditional probability between images
Authors: Ramachandran Suchitra , Meyer Travis , Olson Carl R.
Published: November 2015

When monkeys view two images in fixed sequence repeatedly over days and weeks, neurons in area TE of the inferotemporal cortex come to exhibit prediction suppression. The trailing image elicits only a weak response when presented following the leading image that preceded it during training. Induction of prediction suppression might depend either on the contiguity of the images, as determined by their co-occurrence and captured in the measure of joint probability P( A, B), or on their contingency, as determined by their correlation and as captured in the measures of conditional probability P( A| B) and P( B| A). To distinguish between these possibilities, we measured prediction suppression after imposing training regimens that held P( A, B) constant but varied P( A| B) and P( B| A). We found that reducing either P( A| B) or P( B| A) during training attenuated prediction suppression as measured during subsequent testing. We conclude that prediction suppression depends on contingency, as embodied in the predictive relations between the images, and not just on contiguity, as embodied in their co-occurrence.
Mechanical sensibility of nociceptive and non-nociceptive fast-conducting afferents is modulated by skin temperature
Authors: Boada M. Danilo , Eisenach James C. , Ririe Douglas G.
Published: November 2015

The ability to distinguish mechanical from thermal input is a critical component of peripheral somatosensory function. Polymodal C fibers respond to both stimuli. However, mechanosensitive, modality-specific fast-conducting tactile and nociceptor afferents theoretically carry information only about mechanical forces independent of the thermal environment. We hypothesize that the thermal environment can nonetheless modulate mechanical force sensibility in fibers that do not respond directly to change in temperature. To study this, fast-conducting mechanosensitive peripheral sensory fibers in male Sprague-Dawley rats were accessed at the soma in the dorsal root ganglia from T11 or L4/L5. Neuronal identification was performed using receptive field characteristics and passive and active electrical properties. Neurons responded to mechanical stimuli but failed to generate action potentials in response to changes in temperature alone, except for the tactile mechanical and cold sensitive neurons. Heat and cold ramps were utilized to determine temperature-induced modulation of response to mechanical stimuli. Mechanically evoked electrical activity in non-nociceptive, low-threshold mechanoreceptors (tactile afferents) decreased in response to changes in temperature while mechanically induced activity was increased in nociceptive, fast-conducting, high-threshold mechanoreceptors in response to the same changes in temperature. These data suggest that mechanical activation does not occur in isolation but rather that temperature changes appear to alter mechanical afferent activity and input to the central nervous system in a dynamic fashion. Further studies to understand the psychophysiological implications of thermal modulation of fast-conducting mechanical input to the spinal cord will provide greater insight into the implications of these findings.
Oculomotor selection underlies feature retention in visual working memory
Authors: Hanning Nina M. , Jonikaitis Donatas , Deubel Heiner , Szinte Martin
Published: November 2015

Oculomotor selection, spatial task relevance, and visual working memory (WM) are described as three processes highly intertwined and sustained by similar cortical structures. However, because task-relevant locations always constitute potential saccade targets, no study so far has been able to distinguish between oculomotor selection and spatial task relevance. We designed an experiment that allowed us to dissociate in humans the contribution of task relevance, oculomotor selection, and oculomotor execution to the retention of feature representations in WM. We report that task relevance and oculomotor selection lead to dissociable effects on feature WM maintenance. In a first task, in which an object's location was encoded as a saccade target, its feature representations were successfully maintained in WM, whereas they declined at nonsaccade target locations. Likewise, we observed a similar WM benefit at the target of saccades that were prepared but never executed. In a second task, when an object's location was marked as task relevant but constituted a nonsaccade target (a location to avoid), feature representations maintained at that location did not benefit. Combined, our results demonstrate that oculomotor selection is consistently associated with WM, whereas task relevance is not. This provides evidence for an overlapping circuitry serving saccade target selection and feature-based WM that can be dissociated from processes encoding task-relevant locations.
Clinical Significance of Human Metapneumovirus in Refractory Status Epilepticus and Encephalitis: Case Report and Review of the Literature
Authors: Vehapoglu Aysel , Turel Ozden , Uygur Sahin Turkan , Kutlu Nurettin Onur , Iscan Akın
Published: November 2015

Encephalitis is a complex neurological disease that is associated with significant morbidity and mortality, and the etiology of the disease is often not identified. Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. Few reports are available showing possible involvement of hMPV in development of neurologic complications. Here, we describe an infant, the youngest case in literature, with refractory status epilepticus and severe encephalitis in whom hMPV was detected in respiratory samples and review diagnostic workup of patient with encephalitis.
Topical Anti-Inflammatory Activity of Oil fromTropidurus hispidus(Spix, 1825)
Authors: Santos Israel J. M. , Leite Gerlânia O. , Costa José Galberto M. , Alves Romulo R. N. , Campos Adriana R. , Menezes Irwin R. A. , Freita Francisco Ronaldo V. , Nunes Maria Janeth H. , Almeida Waltécio O.
Published: November 2015

Tropidurus hispidushas been used in traditional medicine in several regions of Northeastern Region of Brazil. Its medicinal use involves the treatment of diseases such as warts, sore throat, tonsillitis, chicken pox, varicella, measles, asthma, alcoholism, and dermatomycosis. The present study evaluated the topical anti-inflammatory activity ofTropidurus hispidusfat in treating ear edema in an animal model. Oil fromT. hispidus(OTH) was evaluated on its effect against experimental inflammation in mice. OTH was extracted from body fat located in the ventral region ofTropidurus hispidususing hexane as a solvent. We used the model of mouse ear edema induced by phlogistic agents, croton oil (single and multiple applications), arachidonic acid, phenol, capsaicin, and histamine, applied into the right ears of animals pretreated with acetone (control), dexamethasone, or OTH. OTH inhibited the dermatitis induced by all noxious agents, except capsaicin. This effect may be related to the fatty acids present in OTH.
Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram
Authors: Moinuddin Irfan , Bracamonte Erika , Thajudeen Bijin , Sussman Amy , Madhrira Machaiah , Costello James
Published: November 2015

Allergic interstitial nephritis (AIN) is an underdiagnosed cause of acute kidney injury (AKI). Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI) as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI.
The Room as Metaphor: Next-of-Kin’s Experiences in End-of-Life Care
Authors: Werkander Harstäde Carina , Roxberg Åsa
Published: November 2015

The “room” in end-of-life is a phenomenon that needs deeper understanding as it is a dimension that shows how health and suffering are shaped. Research on the concept of room was chosen as theoretical foundation in this study in order to reach a profound understanding of the next-of-kin’s “room” in end-of-life care. Lassenius’s hermeneutic interpretation in metaphorical language was used as an deductive-inductive approach to the empirical data. The data material comprised 33 interviews with next-of-kin about their experiences of end-of-life care when being close to a relative dying from a cancer disease. The analysis of the data formed four cases: the Standby, the Asylum, the Wall, and the Place. These cases lend their voices to the experiences of the next-of-kin in the study. The findings of this study explain and may well assist nurses to understand the experiences of being next-of-kin in end-of-life care as forming a room of rest from the suffering, a room of controlling the suffering, a room of hiding from the suffering, and a room of belonging.
Exploration of Prominent Frequency Wave in EEG Signals from Brain Sensors Network
Authors: Mehmood Raja Majid , Lee Hyo Jong
Published: November 2015

We investigated the signals regularity of electroencephalography (EEG) channels separately and determined the energy of selected frequency waves, such as, δ, θ, α, β, and γ. The goal of this research is to identify the prominent frequency band from selected frequencies. We recorded the EEG signal data of 30 controlled subjects with 18 EEG channels. These subjects are all males with an average age of 24 years. Emotional stimuli related to different emotions were presented to each of selected candidates. EEG data were extracted and further processed for artifact removal, filtering, epoch selection and averaging of the signals. We designed and tested our method for exploring the frequency waves of all EEG channels. We also employed the Hjorth parameters to measure the signal regularity in time and frequency domain. The detailed physiological response of human subjects is also presented in this paper. Our results showed that the energy level of delta wave is mostly high in all cases.
A Novel Coupled Resonator Photonic Crystal Design in Lithium Niobate for Electrooptic Applications
Authors: Ozturk Birol , Yavuzcetin Ozgur , Sridhar Srinivas
Published: November 2015

High-aspect-ratio photonic crystal air-hole fabrication on bulk Lithium Niobate (LN) substrates is extremely difficult due to its inherent resistance to etching, resulting in conical structures and high insertion losses. Here, we propose a novel coupled resonator photonic crystal (CRPC) design, combining a coupled resonator approach with that of Bragg gratings. CRPC design parameters were optimized by analytical calculations and FDTD simulations. CRPC structures with optimized parameters were fabricated and electrooptically tested on bulk LN annealed proton exchange waveguides. Low insertion loss and large electrooptic effect were observed with the fabricated devices, making the CRPC design a promising structure for electrooptic device applications.
Protective Effects of Salidroside on Mitochondrial Functions against Exertional Heat Stroke-Induced Organ Damage in the Rat
Authors: Zhang Wei , Peng Ming , Yang Yang , Xiao Zhangwu , Song Bin , Lin Zhaofen
Published: November 2015

Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. The present study was designed to evaluate the protective effects of salidroside on EHS by improving mitochondrial functions in the rat model. Liver and heart mitochondria were observed by transmission electron microscopy and mitochondrial membrane potential (ΔΨm) was detected by a fluorescent probe. Intramitochondrial free Ca2+concentration, mitochondrial respiratory control ratio (RCR), reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and malondialdehyde (MDA) activity were detected by the corresponding kits. RT-PCR was performed to estimate peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α) and manganese form of SOD (MnSOD) mRNA expression. The results demonstrated that salidroside was able to relieve EHS damage by reducing the swelling of mitochondria, ROS levels, and MDA activity, as well as increasing ΔΨm, RCR, free Ca2+concentration, SOD, PGC-1α, and MnSOD mRNA levels. In conclusion, salidroside has protective effects on mitochondrial functions against exertional heat stroke-induced organ damage in the rat.
Broad Protein Spectrum in Stored Pollen of Three Stingless Bees from the Chaco Dry Forest in South America (Hymenoptera, Apidae, Meliponini) and Its Ecological Implications
Authors: Vossler Favio Gerardo
Published: November 2015

Protein content of pollen stored by three meliponine species was variable from 9.78% (less than half the value considered as optimal to brood development inApis mellifera) in typeCapparis tweediana-C. speciosato more than 26% in typeMaytenus vitis-idaeaand someProsopissamples. This pollen of low protein value was occasionally foraged (only six out of 75 masses analyzed ofG. argentina, but none in 86 masses ofT. fiebrigior in ten ofM. orbignyi). However, it is likely that amino acid deficiencies of certain pollens are compensated by randomly foraging on a broad spectrum of pollen plants. The large amounts of pollen stored in their nests might also be important in compensating these deficiencies. The only sample studied forM. orbignyishowed a protein value greater than the one required forA. melliferaand was dominated by typesAcacia praecoxandProsopis. As this species also prefersSolanumand other protein-rich pollen, more samples would need to be analyzed to establish whether protein requirements are high for thisMeliponaspecies. Pollen showing the highest protein content (>26%) belonged to highly nectariferous plants well represented in meliponine andApishoney such asProsopis,Maytenus, andZiziphus.
Interdisciplinary Management of Gingivitis Artefacta Major: A Case Series
Authors: Pattnaik Naina , Satpathy Anurag , Mohanty Rinkee , Nayak Rashmita , Sahoo Surjeet
Published: November 2015

Cases described here discuss interdisciplinary (periodontal and behavioral) approach in the management of rare and difficult to diagnose self-inflicted injuries of gingiva such as gingivitis artefacta major. Self-inflicted injuries to the gingiva are rare and their management by periodontal therapy alone is inadequate. Proper management of this condition requires early detection and effective psychological treatment through behavioral therapy in addition to the treatment of dental lesion. Three male patients in their twenties presented with traumatic injuries of gingiva with history of self-injury and underlying emotional disturbances. Following basic periodontal intervention, their self-inflicting behavior was confirmed on psychiatric consultation. All of them underwent cognitive behavior therapy and were able to successfully curb their self-inflicting behavior prior to any definitive dental procedures. These cases illustrate the essentiality of behavioral intervention in addition to periodontal procedures in the management of such lesions.
A Systematic Literature Review of Three Modalities in Technologically Assisted TKA
Authors: Leone William A. , Elson Leah C. , Anderson Christopher R.
Published: November 2015

In effort to reduce the revision burden of total knee arthroplasty (TKA), industry emphasis has focused on replacing manual techniques—which are subject to variability—with technological implements. Unfortunately, technological innovation often continues before adequate time for critical evaluation has passed. Therefore, the purpose of this descriptive literature review was to collect a large sample of international data and report on the clinical and economic efficacy of three major types of technologically assisted TKA: navigation, patient-specific instrumentation, and sensorized trials.
Increased Avidity of theSambucus nigraLectin-Reactive Antibodies to the Thomsen-Friedenreich Antigen as a Potential Biomarker for Gastric Cancer
Authors: Kurtenkov Oleg , Klaamas Kersti
Published: November 2015

Aim. To determine whether the naturally occurring Thomsen-Friedenreich (TF) antigen-specific antibodies differ in avidity between cancer patients and controls to find a novel biomarker for stomach cancer.Methods. Serum samples were taken from patients with cancer and controls. The level of TF-specific antibodies and their sialylation were determined using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specificSambucus nigraagglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope.Results. A significantly higher SNA lectin binding to anti-TF antibodies was found in cancer patients irrespective of disease stage. The avidity of only IgM TF-specific antibodies was significantly higher in cancer patients compared to controls. The SNA-positive anti-TF antibodies of cancer patients showed a significantly higher avidity,P<0.001. The sensitivity and specificity of this increase for gastric cancer were 73.53% and 73.08%, respectively, with a 73.2% diagnostic accuracy. The higher avidity of SNA-reactive anti-TF antibodies was associated with a benefit in survival of stage 3 cancer patients.Conclusion. The SNA-reactive TF-specific antibodies display a significantly higher avidity in gastric cancer patients compared to controls, which can be used as a potential serologic biomarker for gastric cancer. It appears that IgM is the main target responsible for the above changes.
Congenital Bands with Intestinal Malrotation after Propylthiouracil Exposure in Early Pregnancy
Authors: Leung Alexander A. , Yamamoto Jennifer , Luca Paola , Beaudry Paul , McKeen Julie
Published: November 2015

Exposure to propylthiouracil in early pregnancy may be associated with an increased risk of birth defects. But the spectrum of associated congenital anomalies is not yet well defined. While preliminary reports suggest that most cases of propylthiouracil-associated birth defects are restricted to the preauricular and urinary systems, careful consideration should be given to other possible manifestations of teratogenicity. We propose that congenital bands may potentially represent a rare yet serious complication of propylthiouracil exposure in early pregnancy, possibly arising from an early mesenteric developmental anomaly. We report a case of a 17-day-old girl that presented with acute small bowel obstruction associated with intestinal malrotation arising from several anomalous congenital bands. Her mother was treated for Graves’ disease during pregnancy with first trimester exposure to propylthiouracil but remained clinically and biochemically euthyroid at conception and throughout the duration of pregnancy. This case suggests that the use of propylthiouracil in early pregnancy may be associated with congenital bands and intestinal malrotation. More reports are needed to further support this association.
Association of Pre-miR-146a rs2910164 Polymorphism with Papillary Thyroid Cancer
Authors: Zhang Xin , Gu Yulu , Liu Xiaoli , Yu Yaqin , Shi Jieping , Yu Qiong , Sun Hui , Kanu Joseph Sam , Zhan Siyan , Liu Yawen
Published: November 2015

The incidence rate of papillary thyroid cancer (PTC) has increased over the past decades, but the pathogenesis remains unclear. rs2910164, located in pre-miR-146a, has been studied in PTCs with different ethnicity, but the results were inconsistent. Here we evaluate the association between rs2910164 polymorphism and PTC and investigate the effect of this polymorphism on patients’ clinicopathological characteristics. 1238 PTC patients and 1275 controls, all Han population, from Northern China, were included in our study. rs2910164 was genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Analysis of inheritance model was performed using the SNPStats program. Strength of association was assessed by odds ratio (OR) and 95% confidence interval (CI). Overall, no statistical difference in rs2910164 genotype distribution and allelic frequencies between cases and controls was found, and patients with different genotypes had similar clinicopathological characteristics in terms of stage, location, concurrent of benign thyroid tumor, and thyroiditis, while, as the number of G alleles increased, proportion of patients aged ≥45 years and those without metastasis increased (Ptrend<0.001andPtrend=0.003, resp.). However, no association remained significant after Bonferroni correction under any model of inheritance. Our results suggest no association between rs2910164 polymorphism with PTC and patients’ clinicopathological characteristics.
Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
Authors: Li Xiang-Yun , Mei Guang-Hai , Dong Qiang , Zhang Yu , Guo Zhuang-Li , Su Jing-Jing , Tang Yu-Ping , Jin Xue-Hong , Zhou Hou-Guang , Huang Yan-Yan
Published: November 2015

Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson’s disease (PD).Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082).Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa.Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson’s disease, including rats undergoing long-term L-dopa treatment.
Association of Plasma Heat Shock Protein 70, Interleukin 6, and Creatine Kinase Concentrations in a Healthy, Young Adult Population
Authors: Contreras-Sesvold Carmen , Revenis Bradley D. , O’Connor Francis G. , Deuster Patricia A.
Published: November 2015

Variations of baseline plasma concentrations of creatine kinase (CK), heat shock protein 70 (HSP70), and interleukin 6 (IL-6) have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants—CKMM Nco1 (rs1803285), HSPA1B +A1538G (rs1061581), and IL6 G-174C (rs1800795)—self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29%) in males (1.92 ± 0.08 pg/mL) and higher (29%) among African Americans (2.85 ± 0.50 pg/mL) relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL) was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population.
Impact of Impulse Control Disorders on Sleep-Wake Regulation in Parkinson’s Disease
Authors: Djamshidian Atbin , Poewe Werner , Högl Birgit
Published: November 2015

Sleep disturbances are common in patients with Parkinson’s disease (PD) and are even more prevalent in patients with behavioural addictions, such as pathological gambling, compulsive sexual behaviour, compulsive buying, binge eating, punding, and the compulsive use of dopamine replacement therapy. An overview of the relationship between these impulse control disorders and sleep disturbances is given and potential underlying mechanisms and treatment strategies are covered.
Fibulin-5 Blocks Microenvironmental ROS in Pancreatic Cancer
Authors: Wang Miao , Topalovski Mary , Toombs Jason E. , Wright Christopher M. , Moore Zachary R. , Boothman David A. , Yanagisawa Hiromi , Wang Huamin , Witkiewicz Agnieszka , Castrillon Diego H. , Brekken Rolf A.
Published: November 2015

Elevated oxidative stress is an aberration seen in many solid tumors, and exploiting this biochemical difference has the potential to enhance the efficacy of anticancer agents. Homeostasis of reactive oxygen species (ROS) is important for normal cell function, but excessive production of ROS can result in cellular toxicity, and therefore ROS levels must be balanced finely. Here, we highlight the relationship between the extracellular matrix and ROS production by reporting a novel function of the matricellular protein Fibulin-5 (Fbln5). We used genetically engineered mouse models of pancreatic ductal adenocarcinoma (PDAC) and found that mutation of the integrin-binding domain of Fbln5 led to decreased tumor growth, increased survival, and enhanced chemoresponse to standard PDAC therapies. Through mechanistic investigations, we found that improved survival was due to increased levels of oxidative stress in Fbln5-mutant tumors. Furthermore, loss of the Fbln5–integrin interaction augmented fibronectin signaling, driving integrin-induced ROS production in a 5-lipooxygenase–dependent manner. These data indicate that Fbln5 promotes PDAC progression by functioning as a molecular rheostat that modulates cell–ECM interactions to reduce ROS production, and thus tip the balance in favor of tumor cell survival and treatment-refractory disease. Cancer Res; 75(23); 5058–69. ©2015 AACR.
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Authors: Nilsson Monique B. , Giri Uma , Gudikote Jayanthi , Tang Ximing , Lu Wei , Tran Hai , Fan Youhong , Koo Andrew , Diao Lixia , Tong Pan , Wang Jing , Herbst Roy , Johnson Bruce E. , Ryan Andy , Webster Alan , Rowe Philip , Wistuba Ignacio I. , Heymach John V.
Published: November 2015

Purpose: VEGF pathway inhibitors have been investigated as therapeutic agents in the treatment of non–small cell lung cancer (NSCLC) because of its central role in angiogenesis. These agents have improved survival in patients with advanced NSCLC, but the effects have been modest. Although VEGFR2/KDR is typically localized to the vasculature, amplification of KDR has reported to occur in 9% to 30% of the DNA from different lung cancers. We investigated the signaling pathways activated downstream of KDR and whether KDR amplification is associated with benefit in patients with NSCLC treated with the VEGFR inhibitor vandetanib.

Methods: NSCLC cell lines with or without KDR amplification were studied for the effects of VEGFR tyrosine kinase inhibitors (TKI) on cell viability and migration. Archival tumor samples collected from patients with platinum-refractory NSCLC in the phase III ZODIAC study of vandetanib plus docetaxel or placebo plus docetaxel (N = 294) were screened for KDR amplification by FISH.

Results: KDR amplification was associated with VEGF-induced activation of mTOR, p38, and invasiveness in NSCLC cell lines. However, VEGFR TKIs did not inhibit proliferation of NSCLC cell lines with KDR amplification. VEGFR inhibition decreased cell motility as well as expression of HIF1α in KDR-amplified NSCLC cells. In the ZODIAC study, KDR amplification was observed in 15% of patients and was not associated with improved progression-free survival, overall survival, or objective response rate for the vandetanib arm.

Conclusions: Preclinical studies suggest KDR activates invasion but not survival pathways in KDR-amplified NSCLC models. Patients with NSCLC whose tumor had KDR amplification were not associated with clinical benefit for vandetanib in combination with docetaxel. Clin Cancer Res; 22(8); 1940–50. ©2015 AACR.
Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo
Authors: Madka Venkateshwar , Mohammed Altaf , Li Qian , Zhang Yuting , Biddick Laura , Patlolla Jagan M.R. , Lightfoot Stan , Towner Rheal A. , Wu Xue-Ru , Steele Vernon E. , Kopelovich Levy , Rao Chinthalapally V.
Published: November 2015

Urothelial tumors, accompanied by mutations of the tumor suppressor protein TP53 and dysregulation of mTOR signaling, are frequently associated with aggressive growth and invasiveness. We investigated whether targeting these two pathways would inhibit urothelial tumor growth and progression. Six-week-old transgenic UPII-SV40T male mice (n = 15/group) were fed control diet (AIN-76A) or experimental diets containing mTOR inhibitor (rapamycin, 8 or 16 ppm), p53 stabilizing agent [CP31398 (CP), 150 ppm], or a combination. Mice were euthanized at 40 weeks of age. Urinary bladders were collected and evaluated to determine tumor weight and histopathology. Each agent alone, and in combination, significantly inhibited tumor growth. Treatment with rapamycin alone decreased tumor weight up to 67% (P < 0.0001). Similarly, CP showed approximately 77% (P < 0.0001) suppression of tumor weight. The combination of low-dose rapamycin and CP led to approximately 83% (P < 0.0001) inhibition of tumor weight. There was no significant difference in tumor weights between rapamycin and CP treatments (P > 0.05). However, there was a significant difference between 8 ppm rapamycin and the combination treatment. Tumor invasion was also significantly inhibited in 53% (P < 0.005) and 66% (P < 0.0005) mice after 8 ppm and 16 ppm rapamycin, respectively. However, tumor invasion was suppressed in 73% (P < 0.0001) mice when CP was combined with 8 ppm rapamycin. These results suggest that targeting two or more pathways achieve better treatment efficacy than a single-agent high-dose strategy that could increase the risk of side effects. A combination of CP and rapamycin may be a promising method of inhibiting muscle-invasive urothelial transitional cell carcinoma. Cancer Prev Res; 9(1); 53–62. ©2015 AACR.
Lateral Thalamic Infarction and the Vascular Geometry of the Posterior Cerebral Artery
Authors: Kim Bum Joon , Kim Seung Min , Ahn Sung-ho , Kang Dong-Wha , Kwon Sun U. , Kim Jong S.
Published: November 2015

Background: The geometric properties of the parental artery affect the development of local atherosclerosis and perforator infarction. In this study, we aimed at investigating the association between vascular geometry of the posterior cerebral artery (PCA) and the development of isolated lateral thalamic infarction (LTI), the most frequent type of thalamic infarction. Methods: The geometric properties of the corresponding PCA in LTI patients were assessed and they include the diameters of the distal basilar artery (BA) and proximal PCA, distal BA - PCA angle, first PCA angle (angle between P1 and P2), and the presence of the posterior communicating artery (Pcom). These parameters obtained from the ipsilesional PCA were compared with the contralesional PCA and the corresponding PCA in age- and sex-matched controls. Results: Forty-five LTI patients were enrolled. The ipsilesional PCA in LTI patients demonstrated a greater ipsilesional P1 - P2 angle (81.4 ± 22.6 vs. 71.3 ± 23.2°, respectively; p = 0.04) and a higher prevalence of Pcom (42.2 vs. 13.3%; p = 0.002) when compared to control subjects. In comparison with the contralesional PCA, ipsilesional PCA demonstrated a smaller diameter, larger angle between P1 and P2 segment, and a higher prevalence of Pcom. The presence of hyperlipidemia (OR 3.548 (1.283-9.811); p = 0.02) and Pcom (OR 3.507 (1.104-11.135); p = 0.03) was a factor that was independently associated with LTI. Conclusions: Local hemodynamics in the PCA may be influenced by the P1 - P2 angle and the presence of Pcom, which are associated with the development of LTI.
Evaluation of ART Scores for Repeated Transarterial Chemoembolization in Japanese Patients with Hepatocellular Carcinoma
Authors: Arizumi Tadaaki , Ueshima Kazuomi , Iwanishi Mina , Minami Tomohiro , Chishina Hirokazu , Kono Masashi , Takita Masahiro , Kitai Satoshi , Inoue Tatsuo , Yada Norihisa , Hagiwara Satoru , Ida Hiroshi , Minami Yasunori , Sakurai Toshiharu , Nishida Naoshi , Kitano Masayuki , Kudo Masatoshi
Published: November 2015

Objective: Transarterial chemoembolization (TACE) is recommended as a first-line therapy for hepatocellular carcinoma (HCC) patients ineligible for curative therapy and without portal invasion. The Assessment for Retreatment with TACE (ART) scoring system was recently proposed for identifying patients who would not show sufficient survival benefit from repeated TACE. We reevaluated the performance of ART in HCC patients treated in Japan, where selective TACE is commonly used. Methods: Between 2000 and 2013, 988 patients with HCC underwent TACE at Kinki University Hospital, and 627 received ≥2 sessions of TACE. Seventy-six patients who underwent ≥2 TACE sessions within 90 days were investigated for their performance of the ART score in the context of overall survival (OS). Results: Only 12% (76/627) of patients underwent ≥2 TACE sessions within 90 days. Of those, 52 patients showed a low ART score (0-1.5), and 24 had a high ART score (≥2.5); the median OS was 20.2 and 37.6 months, respectively (p = 0.8207). Conclusion: The ART scoring system did not demonstrate a sufficiently predictive impact on OS among the patients who underwent ≥2 TACE sessions within 90 days. Application of the ART score should be carefully considered because differences in TACE procedures and post-TACE treatment can affect the results while evaluating OS.
Validation of a Modified Substaging System (Kinki Criteria) for Patients with Intermediate-Stage Hepatocellular Carcinoma
Authors: Arizumi Tadaaki , Ueshima Kazuomi , Iwanishi Mina , Minami Tomohiro , Chishina Hirokazu , Kono Masashi , Takita Masahiro , Kitai Satoshi , Inoue Tatsuo , Yada Norihisa , Hagiwara Satoru , Ida Hiroshi , Minami Yasunori , Sakurai Toshiharu , Kitano Masayuki , Nishida Naoshi , Kudo Masatoshi
Published: November 2015

Introduction: Barcelona Clinic Liver Cancer (BCLC) stage B, an intermediate stage, includes various conditions of hepatocellular carcinoma (HCC). This heterogeneity of the patients with intermediate-stage HCC makes it difficult to predict their survival rates. In the present study, we examined the validity of the modified Bolondi classification (Kinki criteria) as a subclassification of patients with BCLC stage B HCC. Methods: Of 906 patients who underwent conventional transarterial chemoembolization at Kinki University Hospital, 753, who met the inclusion criteria, were examined. Of these 753 patients, 425 (56.4%) with BCLC stage B were subclassified using the Kinki criteria to examine the survival rate. Results: According to the Kinki criteria, 158 (37.2%) were subclassified into subclass B1, 236 (55.5%) into B2, and 31 (7.3%) into B3. The comparison of the survival rates showed that the median overall survival was 3.9 years (95% CI, 3.2-4.6) in the BCLC subclass B1 group, 2.5 years (95% CI, 2.2-3.1) in the B2 group, and 1.1 years (95% CI, 0.6-1.5) in the B3 group (p < 0.001). Conclusion: When the BCLC stage B patients were subclassified according to the Kinki criteria, survival curves were stratified with significant differences, suggesting that the Kinki criteria were suitable for the subclassification of the intermediate-stage HCC patients.
High-Intensity Signal in Carotid Plaque on Routine 3D-TOF-MRA Is a Risk Factor of Ischemic Stroke
Authors: Yamada Kiyofumi , Kawasaki Masanori , Yoshimura Shinichi , Shirakawa Manabu , Uchida Kazutaka , Shindo Seigo , Nishida Shuji , Iwamoto Yasuhiro , Nakahara Shigehiro , Sato Yoshikazu
Published: November 2015

Background: Carotid atherosclerotic disease is recognized as an important risk factor for brain ischemic events. However, high-grade stenosis does not always cause ischemic strokes, whereas moderate-grade stenosis may often cause ischemic strokes. It has been reported that there is an association between carotid intraplaque hemorrhage (IPH) and new cerebral ischemic events. The purpose of this study was to elucidate the relationship between high-intensity signals (HIS) on maximum intensity projection (MIP) images from routine 3-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and prior ischemic strokes in the patients with moderate carotid stenosis. Materials and Methods: Sixty-one patients with moderate carotid artery stenosis (50-69% stenosis based on North American Symptomatic Carotid Endarterectomy Trial criteria) were included. Carotid IPH was defined as the presence of HIS in carotid plaques on MIP images detected by 3D-TOF-MRA using criteria we previously reported. We analyzed the relationship between the presence of HIS in plaques and prior ischemic strokes defined as ischemic lesions on diffusion-weighted brain images. Results: HIS in carotid plaques were present in 27 (44%) of 61 patients. Prior ipsilateral ischemic strokes occurred more frequently in the HIS-positive group than the HIS-negative group (67 vs. 9%, p < 0.001). Furthermore, there were more smokers in the group with ischemic stroke than without it (62 vs. 25%, p = 0.005). In multivariate logistic regression analysis, HIS in carotid plaque (OR 23.4, 95% CI 4.62-118.3, p < 0.001) and smoking (OR 5.44, 95% CI 1.20-24.6, p = 0.028) were independent determinants of prior ischemic strokes after adjustment for age. Conclusions: HIS in carotid plaques on 3D-TOF-MRA MIP images are independent determinants of prior ischemic strokes in patients with moderate carotid artery stenosis, and they can potentially provide a reliable risk stratification of patients with moderate carotid artery stenosis.
Scalp Psoriasiform Contact Dermatitis with Acute Telogen Effluvium due to Topical Minoxidil Treatment
Authors: La Placa Michelangelo , Balestri Riccardo , Bardazzi Federico , Vincenzi Colombina
Published: November 2015

Topical minoxidil, the only approved treatment for female pattern hair loss (FPHL), has been associated with scalp allergic contact dermatitis (ACD). We report the case of 2 female patients who developed ACD from minoxidil solution with severe telogen effluvium and psoriasiform scalp dermatitis. Scalp dermoscopy was useful to identify the psoriasiform vascular pattern, whereas patch testing made it possible to differentiate the cause of sensitization. In one case, minoxidil was the sole cause of scalp dermatitis, while in the other patient it was only the vehicle, thus permitting the patient to continue the treatment for FPHL.
Malignant MCA Infarction: Pathophysiology and Imaging for Early Diagnosis and Management Decisions
Authors: Heiss Wolf-Dieter
Published: November 2015

Background: Malignant middle cerebral artery infarction is a devastating condition, with up to 80% mortality in conservatively treated patients. The pathophysiology of this stroke is characterized by a large core of severe ischemia and only a relatively small rim of penumbra. Due to the fast development of irreversible morphological damage, cytotoxic edema occurs immediately in a large portion of the ischemic territory. The subsequent damage of the tight junctions leads to the breakdown of the blood brain barrier and vasogenic brain edema, resulting in space-occupying brain swelling. The progressive vasogenic edema reaches its maximum after 1 to several days and exerts a mechanical force on surrounding tissue structures leading to midline shift and transtentorial herniation and finally brain stem compression and death. Summary: Early severe neurological symptoms - hemiparesis, gaze deviation, higher cortical signs - followed by headache, vomiting, papillo edema and reduced consciousness may predict the deleterious course. Imaging supports the suspected diagnosis with hypodense changes on CT extending beyond 50% of the MCA territory. The size of the probably infarcted tissue and a midline shift on CT as well as the size of the lesion on diffusion-weighted MRI are predictive of a malignant course. Reduction of cerebral blood flow below a critical value and volume of irreversible tissue damage detected by positron emission tomography in the early hours after the stroke are indicative of progression to malignant infarction with increased intracranial pressure (ICP) and decreased tissue oxygen tension observed by multimodal neuromonitoring in the later course. Treatment options of malignant infarction include general measures to limit the extent of space-occupying edema, but these therapies have not been efficacious. Only surgical intervention with decompressive hemicraniectomy (DHC) was successful in relieving the effects of increased ICP and of the deleterious shifts of brain tissue. Several controlled clinical trials have proven the efficacy of DHC with a significant decrease in mortality and improved functional outcome. However, DHC must be performed early and with a large diameter, regardless of the age of patients, but in patients beyond 60 years, the higher likelihood of resulting severe disability should be taken into consideration. Key Messages: Malignant MCA infarction can be predicted early with a high sensitivity by neuroimaging. The early diagnosis is mandatory for DHC, which was shown to reduce mortality and improve functional outcome in several controlled clinical trials.
Impact of Collateral Status on Successful Revascularization in Endovascular Treatment: A Systematic Review and Meta-Analysis
Authors: Leng Xinyi , Fang Hui , Leung Thomas W.H. , Mao Chen , Xu Yuming , Miao Zhongrong , Liu Liping , Wong K.S. Lawrence , Liebeskind David S.
Published: November 2015

Background: Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic review and meta-analysis to synthesize relevant evidence currently available. Methods: Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT. Results: In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities. Conclusions: Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients.
Isonatric Dialysis Biofeedback in Hemodiafiltration with Online Regeneration of Ultrafiltrate in Hypertensive Hemodialysis Patients: A Randomized Controlled Study
Authors: Chevalier Louise , Tielemans Christian , Debelle Frederic , Vandervelde Dominique , Fumeron Christine , Mandart Lise , Stolear Jean-Claude , Simon Isabelle , Delmas Yahsou , Testa Angelo , Mat Olivier , Tezenas du Montcel Sophie , Mercadal Lucile
Published: November 2015

Dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR) could help to improve arterial hypertension. We evaluated the impact of isonatric HFR (HFR-iso) on hypertension control compared to conventional HFR. Forty-seven hemodialysis patients were included and randomized (ratio 2/1) HFR-iso versus HFR during 24 dialysis sessions. In the HFR-iso group (32 patients, 768 dialysis sessions), the predialytic systolic blood pressure (BP) decreased from S1 to S24 of 9 ± 20 mm Hg and increased of 5 ± 24 mm Hg in the HFR group (15 patients, 360 dialysis sessions), variation that differed between the 2 groups (ΔS1-S24, p = 0.035; interaction group*time, p = 0.012). The diastolic BP (HFR-iso -3 ± 14 mm Hg vs. HFR 5 ± 13 mm Hg; p = 0.088), the DDD of antihypertensive treatment and the dry weight did not vary significantly during the study. Number of sessions complicated by symptomatic hypotension was similar in the 2 groups. HFR-iso improved BP control without increasing dialysis hypotension episodes. Short Summary: In this multicenter, open-label, controlled, randomized study, we evaluated the impact of dialysis biofeedback in HFR on arterial hypertension compared to conventional HFR. We observed that HFR-iso improved arterial BP control without increasing dialysis hypotension episodes.
Multiple HPV-Induced Squamous Cell Carcinomas on the Fingers of a Patient with Systemic Lupus Erythematosus: A Case and Review
Authors: Nikolakis Georgios , Karagiannidis Ioannis , Zampeli Vasiliki A. , Altenburg Andreas , Brunner Martina , Zouboulis Christos C.
Published: November 2015

Human papilloma virus (HPV) infection is documented to be involved in the development of epithelial malignancies, mostly in cervical cancer. Systemic lupus erythematosus (SLE) patients have an increased prevalence of such an infection. We report the case of a 55-year-old female SLE patient who developed multiple in situ squamous cell carcinomas on her fingers, after chronic HPV infection. HPV-33 DNA was isolated from the lesions. The purpose of this case presentation is to raise awareness about HPV-induced malignancies for this high-risk group and propose an early HPV vaccination to efficiently prevent such comorbidities.