bluuebunny/crossref_metadata_2025 huggingface dataset:
Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes
Authors: Fan Zhuo , Wen Ting , Chen Yaoxu , Huang Lijie , Lin Wei , Yin Chunxia , Tan Wen
Published: February 2016

KATP channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of KATP channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti‐IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcKATP channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcKATP channels induced by pinacidil but also potentiated diazoxide‐elicited oxidation of flavoprotein in mitochondria.
Electron Paramagnetic Resonance Examination of Free Radical Formation in Salicylic Acid and Urea Exposed to UV Irradiation
Authors: Ramos Paweł , Pilawa Barbara
Published: February 2016

Free radicals formed by UV irradiation of the two magistral formulas applied on the skin, salicylic acid and urea, were examined by X-band (9.3 GHz) EPR spectroscopy. The influence of the time of UVA (315–400 nm) irradiation on free radical properties and concentrations in the drug samples was determined. The nonirradiated magistral formula did not contain free radicals. Amplitudes (A) and linewidths (ΔBpp) of EPR spectra were analysed. Fast spin-lattice relaxation process existed in the tested drugs. UV irradiation did not change spin-lattice interactions in the tested magistral formula. Concentrations of free radicals formed by UV irradiation in salicylic acid and urea were ~1017–1018 spins/g. The strongest formation of free radicals under UV irradiation was observed for salicylic acid than for urea. Free radical concentration in salicylic acid increased with the increase of UV irradiation time from 15 minutes to 30 minutes, and after its value remained unchanged. The increase of free radical concentration in urea with UV irradiation time was stated. Salicylic acid is characterized with higher photosensitivity than urea. Salicylic acid, urea, and the skin treated by them should not be stored on UV exposure. The usefulness of EPR spectroscopy to optimize storage conditions of recipe drugs was conformed.
Autonomous WiFi Sensor for Heating Systems in the Internet of Things
Authors: Trasviña-Moreno C. A. , Blasco R. , Casas R. , Marco A.
Published: February 2016

In smart cities and home applications, the use of Wireless Sensor Networks to extract environmental data becomes more common with the passing of time. These sensors are used for a wide array of applications, but mainly to manage energy consumption in domestic buildings. One of the key energy consumers in households is heating systems. To monitor them, sensors are used with wireless communication protocols, like ZigBee, to transmit data to a central processing unit (CPU). WiFi communications, on the contrary, are rarely seen in these implementations due to its high energy consumption, although almost in every home one can find such networks. Yet, with the Internet of Things (IoT), new revisions of the standard have arisen which enable this technology for wireless sensing. To validate this theory and fill a technological necessity, this proposal is presented. In this work, the design and implementation of an autonomous WiFi sensor, paired with thermoelectric energy harvesting, are presented as an IoT solution for monitoring heating devices. For this, a thorough analysis of the proposed architecture is presented. Tests regarding energy consumption and generation, efficiency, and real world scenario trials are done. Finalizing, a comparison between the obtained results and current implementations is shown.
Wavelet Based Method for Congestive Heart Failure Recognition by Three Confirmation Functions
Authors: Daqrouq K. , Dobaie A.
Published: February 2016

An investigation of the electrocardiogram (ECG) signals and arrhythmia characterization by wavelet energy is proposed. This study employs a wavelet based feature extraction method for congestive heart failure (CHF) obtained from the percentage energy (PE) of terminal wavelet packet transform (WPT) subsignals. In addition, the average framing percentage energy (AFE) technique is proposed, termed WAFE. A new classification method is introduced by three confirmation functions. The confirmation methods are based on three concepts: percentage root mean square difference error (PRD), logarithmic difference signal ratio (LDSR), and correlation coefficient (CC). The proposed method showed to be a potential effective discriminator in recognizing such clinical syndrome. ECG signals taken from MIT-BIH arrhythmia dataset and other databases are utilized to analyze different arrhythmias and normal ECGs. Several known methods were studied for comparison. The best recognition rate selection obtained was for WAFE. The recognition performance was accomplished as 92.60% accurate. The Receiver Operating Characteristic curve as a common tool for evaluating the diagnostic accuracy was illustrated, which indicated that the tests are reliable. The performance of the presented system was investigated in additive white Gaussian noise (AWGN) environment, where the recognition rate was 81.48% for 5 dB.
Outcome of the Pediatric Patients with Portal Cavernoma: The Retrospective Study for 10 Years Focusing on Recurrent Variceal Bleeding
Authors: Guo Hongjie , Hao Fabao , Guo Chunbao , Yu Yang
Published: February 2016

Background. Portal cavernoma (PC) is the most critical condition with risk or variceal hemorrhage in pediatric patients. We retrospectively investigated the patients with PC focusing on the predictors for recurrent variceal bleeding.Methods. Between July 2003 and June 2013, we retrospectively enrolled all consecutive patients admitted to our department with a diagnosis of PC without abdominal malignancy or liver cirrhosis. The primary endpoint of this observational study was recurrent variceal bleeding. Independent predictors of recurrent variceal bleeding were identified using the logistic regression model.Results. A total of 157 patients were enrolled in the study. During the follow-up period, 24 patients exhibited onset of recurrent variceal bleeding. Acute variceal bleeding was subjected to conservative symptomatic treatment and emergency endoscopic sclerotherapy. Surgical procedure selection was based on the severity of vascular dilation and collateral circulation. Multivariate logistic regression analysis demonstrated that the presence of ascites, collateral circulation, and portal venous pressure were independent prognostic factors of recurrent variceal bleeding for patients with portal cavernoma.Conclusions. The presence of ascites, collateral circulation, and portal venous pressure evaluation are important and could predict the postsurgical recurrent variceal bleeding in patients with portal cavernoma.
Development of a Murine Infection Model withLeishmania killicki, Responsible for Cutaneous Leishmaniosis in Algeria: Application in Pharmacology
Authors: Eddaikra Naouel , Kherachi Djenad Ihcene , Benbetka Sihem , Benikhlef Razika , Aït-Oudhia Khatima , Moulti-Mati Farida , Oury Bruno , Sereno Denis , Harrat Zoubir
Published: February 2016

In Algeria,Leishmania infantum,Leishmania major, andLeishmania killicki(Leishmania tropica) are responsible for cutaneous leishmaniosis. We established a murine model ofL. killickiinfection to investigate its infective capacity, some immunophysiopathological aspects, and its suitability for pharmacological purposes. Following the injection ofL. majororL. killickimetacyclic promastigotes in the ear dermis of BALB/c mice, the course of infection was followed. The infection withL. killickicaused slower lesion formation than withL. major. The presence ofL. killickiorL. majorDNA and parasites was detected in the ear dermis and in lymph nodes, spleen, and liver. Lesions induced byL. killickiwere nonulcerative in their aspect, whereas those caused byL. majorwere highly ulcerative and necrotic, which matches well with the lesion phenotype reported in humans forL. killickiandL. major, respectively. The treatment ofL. killickilesions by injection of Glucantime® significantly reduced the lesion thickness and parasite burden. Ear dermal injection of BALB/c mice constitutes a model to study lesions physiopathology caused byL. killickiand presents interest forin vivoscreening of new compounds against this pathogen, emerging in Algeria.
RSV-Related Thrombocytopenia Associated with Transient Cytogenetic Abnormalities in a Recipient of Umbilical Cord Blood Transplantation
Authors: Pokhrel Sabita D. , Persons Diane L. , Aljitawi Omar S.
Published: February 2016

Respiratory syncytial virus (RSV) infections are associated with thrombocytopenia. The underlying mechanism of thrombocytopenia in this setting is unknown. Herein, we report a case of RSV-related thrombocytopenia associated with transient cytogenetic abnormalities that occurred following umbilical cord blood transplantation.
Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas
Authors: Tang Xiaohu , Wu Jianli , Ding Chien-Kuang , Lu Min , Keenan Melissa M. , Lin Chao-Chieh , Lin Chih-An , Wang Charles C. , George Daniel , Hsu David S. , Chi Jen-Tsan
Published: February 2016

Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addicted remains difficult. Here, we performed a nutrigenetic screen to determine the phenotypes of isogenic pairs of clear cell renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids. We found that cystine deprivation triggered rapid programmed necrosis in VHL-deficient cell lines and primary ccRCC tumor cells, but not in VHL-restored counterparts. Blocking cystine uptake significantly delayed xenograft growth of ccRCC. Importantly, cystine deprivation triggered similar metabolic changes regardless of VHL status, suggesting that metabolic responses alone are not sufficient to explain the observed distinct fates of VHL-deficient and restored cells. Instead, we found that increased levels of TNFα associated with VHL loss forced VHL-deficient cells to rely on intact RIPK1 to inhibit apoptosis. However, the preexisting elevation in TNFα expression rendered VHL-deficient cells susceptible to necrosis triggered by cystine deprivation. We further determined that reciprocal amplification of the Src–p38 (MAPK14)–Noxa (PMAIP1) signaling and TNFα–RIP1/3 (RIPK1/RIPK3)–MLKL necrosis pathways potentiated cystine-deprived necrosis. Together, our findings reveal that cystine deprivation in VHL-deficient RCCs presents an attractive therapeutic opportunity that may bypass the apoptosis-evading mechanisms characteristic of drug-resistant tumor cells. Cancer Res; 76(7); 1892–903. ©2016 AACR.
An Integrated Analysis of Heterogeneous Drug Responses in Acute Myeloid Leukemia That Enables the Discovery of Predictive Biomarkers
Authors: Chen Weihsu C. , Yuan Julie S. , Xing Yan , Mitchell Amanda , Mbong Nathan , Popescu Andreea C. , McLeod Jessica , Gerhard Gitte , Kennedy James A. , Bogdanoski Goce , Lauriault Stevan , Perdu Sofie , Merkulova Yulia , Minden Mark D. , Hogge Donna E. , Guidos Cynthia , Dick John E. , Wang Jean C.Y.
Published: February 2016

Many promising new cancer drugs proceed through preclinical testing and early-phase trials only to fail in late-stage clinical testing. Thus, improved models that better predict survival outcomes and enable the development of biomarkers are needed to identify patients most likely to respond to and benefit from therapy. Here, we describe a comprehensive approach in which we incorporated biobanking, xenografting, and multiplexed phospho-flow (PF) cytometric profiling to study drug response and identify predictive biomarkers in acute myeloid leukemia (AML) patients. To test the efficacy of our approach, we evaluated the investigational JAK2 inhibitor fedratinib (FED) in 64 patient samples. FED robustly reduced leukemia in mouse xenograft models in 59% of cases and was also effective in limiting the protumorigenic activity of leukemia stem cells as shown by serial transplantation assays. In parallel, PF profiling identified FED-mediated reduction in phospho-STAT5 (pSTAT5) levels as a predictive biomarker of in vivo drug response with high specificity (92%) and strong positive predictive value (93%). Unexpectedly, another JAK inhibitor, ruxolitinib (RUX), was ineffective in 8 of 10 FED-responsive samples. Notably, this outcome could be predicted by the status of pSTAT5 signaling, which was unaffected by RUX treatment. Consistent with this observed discrepancy, PF analysis revealed that FED exerted its effects through multiple JAK2-independent mechanisms. Collectively, this work establishes an integrated approach for testing novel anticancer agents that captures the inherent variability of response caused by disease heterogeneity and in parallel, facilitates the identification of predictive biomarkers that can help stratify patients into appropriate clinical trials. Cancer Res; 76(5); 1214–24. ©2016 AACR.
Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation
Authors: Hedayati Mohammad , Haffner Michael C. , Coulter Jonathan B. , Raval Raju R. , Zhang Yonggang , Zhou Haoming , Mian Omar , Knight Emma J. , Razavi Nina , Dalrymple Susan , Isaacs John T. , Santos Aileen , Hales Russell , Nelson William G. , Yegnasubramanian Srinivasan , DeWeese Theodore L.
Published: February 2016

Purpose: The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen-deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen-induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR).

Experimental Design: Androgen-induced DNA damage was assessed by comet assays and γH2A.X foci formation. Effects of androgen stimulation and radiation were determined in vitro and in vivo with xenograft models.

Results: We document that androgen treatment of androgen-deprived prostate cancer cell lines resulted in a dose- and time-dependent induction of widespread DSBs. Generation of these breaks was dependent on androgen receptor and topoisomerase II beta but not on cell-cycle progression. In vitro models demonstrated a synergistic interaction between IR and androgen stimulation when IR is given at a time point corresponding with high levels of androgen-induced DSB formation. Furthermore, in vivo studies showed a significant improvement in tumor growth delay when radiation was given shortly after androgen repletion in castrated mice.

Conclusions: These results suggest a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. Clin Cancer Res; 22(13); 3310–9. ©2016 AACR.

See related commentary by Chua and Bristow, p. 3124
Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors
Authors: Macaulay Valentine M. , Middleton Mark R. , Eckhardt S. Gail , Rudin Charles M. , Juergens Rosalyn A. , Gedrich Richard , Gogov Sven , McCarthy Sean , Poondru Srinivasu , Stephens Andrew W. , Gadgeel Shirish M.
Published: February 2016

Purpose: Cross-talk between type I IGF receptor (IGF1R), insulin receptor (INSR), and epidermal growth factor receptor (EGFR) mediates resistance to individual receptor blockade. This study aimed to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of linsitinib, a potent oral IGF1R/INSR inhibitor, with EGFR inhibitor erlotinib.

Experimental Design: This open-label, dose-escalation study investigated linsitinib schedules S1: once daily intermittent (days 1–3 weekly); S2, once daily continuous; S3, twice-daily continuous; each with erlotinib 100–150 mg once daily; and a non–small cell lung cancer (NSCLC) expansion cohort.

Results: Ninety-five patients were enrolled (S1, 44; S2, 24; S3, 12; expansion cohort, 15) and 91 treated. Seven experienced dose-limiting toxicities: QTc prolongation (3), abnormal liver function (2), hyperglycemia (1), and anorexia (1). Common adverse events included drug eruption (84%), diarrhea (73%), fatigue (68%), nausea (58%), vomiting (40%). MTDs for linsitinib/erlotinib were 450/150 mg (S1), 400/100 mg (S2). On the basis of prior monotherapy data, S3 dosing at 150 mg twice daily/150 mg once daily was the recommended phase II dose for the expansion cohort. There was no evidence of drug–drug interaction. Pharmacodynamic data showed IGF-1 elevation and reduced IGF1R/INSR phosphorylation, suggesting pathway inhibition. Across schedules, 5/75 (7%) evaluable patients experienced partial responses: spinal chordoma (268+ weeks), rectal cancer (36 weeks), three NSCLCs including 2 adenocarcinomas (16, 72 weeks), 1 squamous wild-type EGFR NSCLC (36 weeks). Disease control (CR+PR+SD) occurred in 38 of 75 (51%), and 28 of 91 (31%) patients were on study >12 weeks.

Conclusions: The linsitinib/erlotinib combination was tolerable with preliminary evidence of activity, including durable responses in cases unlikely to respond to erlotinib monotherapy. Clin Cancer Res; 22(12); 2897–907. ©2016 AACR.
T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin
Authors: Dziegielewska Barbara , Casarez Eli V. , Yang Wesley Z. , Gray Lloyd S. , Dziegielewski Jaroslaw , Slack-Davis Jill K.
Published: February 2016

Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca2+) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca2+ channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca2+ channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis. Together, the data provide rationale for future use of T-type channel antagonists together with platinum agents for the treatment of ovarian cancer. Mol Cancer Ther; 15(3); 460–70. ©2016 AACR.
EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib
Authors: De Andrade James P. , Park Jung M. , Gu Vivian W. , Woodfield George W. , Kulak Mikhail V. , Lorenzen Allison W. , Wu Vincent T. , Van Dorin Sarah E. , Spanheimer Philip M. , Weigel Ronald J.
Published: February 2016

Expression of TFAP2C in luminal breast cancer is associated with reduced survival and hormone resistance, partially explained through regulation of RET. TFAP2C also regulates EGFR in HER2 breast cancer. We sought to elucidate the regulation and functional role of EGFR in luminal breast cancer. We used gene knockdown (KD) and treatment with a tyrosine kinase inhibitor (TKI) in cell lines and primary cancer isolates to determine the role of RET and EGFR in regulation of p-ERK and tumorigenesis. KD of TFAP2C decreased expression of EGFR in a panel of luminal breast cancers, and chromatin immunoprecipitation sequencing (ChIP-seq) confirmed that TFAP2C targets the EGFR gene. Stable KD of TFAP2C significantly decreased cell proliferation and tumor growth, mediated in part through EGFR. While KD of RET or EGFR reduced proliferation (31% and 34%, P < 0.01), combined KD reduced proliferation greater than either alone (52% reduction, P < 0.01). The effect of the TKI vandetanib on proliferation and tumor growth response of MCF-7 cells was dependent upon expression of TFAP2C, and dual KD of RET and EGFR eliminated the effects of vandetanib. The response of primary luminal breast cancers to TKIs assessed by ERK activation established a correlation with expression of RET and EGFR. We conclude that TFAP2C regulates EGFR in luminal breast cancer. Response to vandetanib was mediated through the TFAP2C target genes EGFR and RET. Vandetanib may provide a therapeutic effect in luminal breast cancer, and RET and EGFR can serve as molecular markers for response. Mol Cancer Ther; 15(3); 503–11. ©2016 AACR.
Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer
Authors: Ishida Michihiro , Kagawa Shunsuke , Shimoyama Kyoko , Takehara Kiyoto , Noma Kazuhiro , Tanabe Shunsuke , Shirakawa Yasuhiro , Tazawa Hiroshi , Kobayashi Hisataka , Fujiwara Toshiyoshi
Published: February 2016

Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer. We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. In vitro, adenovirus/HER2-ECD (Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-IR700 (Tra-IR700)–mediated PIT induced selective cell death of HER2-ECD–transduced tumor cells. Ad/HER2-ECD also induced homogenous expression of HER2 in heterogeneous gastric cancer cells, resulting in uniform sensitivity of the cells to Tra-IR700–mediated PIT. Anti-HER2 PIT integrated with adenoviral HER2-ECD gene transfer was applied in mice bearing peritoneal dissemination of HER2-negative gastric cancer. Intraperitoneal administration of Ad/HER2-ECD and Tra-IR700 with PIT inhibited peritoneal metastasis and prolonged the survival of mice bearing MKN45. Furthermore, minimal side effects allowed the integrated therapy to be used repeatedly, providing better control of peritoneal dissemination. In conclusion, the novel therapy of molecular-targeted PIT integrated with gene transfer technology is a promising approach for the treatment of peritoneal dissemination in gastric cancer. Mol Cancer Ther; 15(3); 402–11. ©2016 AACR.
Successful Treatment of Segmental Vitiligo in Children with the Combination of 1-mm Minigrafts and Phototherapy
Authors: Tsuchiyama Kenichiro , Watabe Akiko , Sadayasu Anna , Onodera Nobue , Kimura Yutaka , Aiba Setsuya
Published: February 2016

Background: Minigrafts using a 1-mm biopsy punch (1-mm minigrafts) are being increasingly used to treat vitiligo. However, there have been few reports of the use of 1-mm minigrafts in pediatric patients. Objective: To examine the effectiveness of combination therapy with 1-mm minigrafts and phototherapy in children with segmental vitiligo. Methods: Minigrafts were placed in 13 patients aged ≤16 years with segmental vitiligo. Following surgery, 11 patients underwent irradiation with excimer laser light and 2 with narrow-band ultraviolet B light. Results: A mean repigmentation of 81.6% was obtained. A particularly high mean repigmentation of 87.9% was seen in patients aged ≤12 years, indicating greater efficacy in these patients than in patients aged ≥13 years (mean, 67.5%). Although a transient cobblestone appearance occurred as an adverse effect, it improved over time. Conclusions: Combined treatment of segmental vitiligo with 1-mm minigrafts and phototherapy can be performed safely and is highly effective in young patients.
The Use of Aspiration Catheter Systems for Embolic Protection during Intracranial Vertebral Artery Angioplasty and Stenting
Authors: Gesheva Silvia I. , Hastings Laurel H. , Wilson Jason D.
Published: February 2016

Background: Posterior circulation strokes comprise approximately 20-25% of all strokes of ischemic origin. Strokes affecting this area carry a significantly higher risk for subsequent stroke or death as compared to anterior circulation strokes. Embolic protection device (EPD) use for carotid artery stenosis has translated into percutaneous interventions of proximal vertebral artery (VA) stenosis. However, the use of EPDs when treating intracranial lesions has yet to be studied and may not be feasible as the vessel caliber is frequently smaller than in existing devices. Objective: The aim of this study is to describe a proximal aspiration technique used during the treatment of intracranial VA and basilar artery (BA) atherosclerotic disease. Methods: Proximal embolic protection was utilized during the treatment of intracranial VA/BA stenosis with angioplasty and stenting in patients with medically refractory disease. Results: Three patients with severe symptomatic posterior circulation stenosis refractory to medical management were treated with angioplasty and stenting utilizing proximal aspiration. Pre- and post-treatment angiograms and MRIs were compared. Treated vascular stenoses were significantly improved, without new neurological deficits or ischemic injury identified on imaging. Conclusions: The proposed technique of proximal embolic protection may help overcome the challenge of embolus propagation inherent to the treatment modality that was encountered during the treatment of intracranial VA/BA stenosis.
Successful Image-Guided Retrieval of an Embolized Fragment of a Fractured Haemodialysis Catheter Tip from the Pulmonary Artery
Authors: Teoh Chia Wei , Thakor Avnesh S. , Amaral Joao G. , Parra Dimitri A. , Harvey Elizabeth A. , Noone Damien G.
Published: February 2016

Background: Cuffed, double-lumen, tunneled haemodialysis catheters are a common means of vascular access in paediatric haemodialysis, particularly in infants. Haemodialysis catheter fracture with distal embolization is a rare complication. Case Report: A 2-year-old boy was receiving chronic haemodialysis via a right internal jugular cuffed, double-lumen, tunneled haemodialysis catheter, inserted 3 months previously. He was asymptomatic and was incidentally found to have had embolization of a fractured catheter tip into a segmental branch of the left pulmonary artery. The catheter was replaced and the embolized fragment successfully retrieved, non-surgically, using an image-guided endovascular approach with a loop snare device. Conclusion: Haemodialysis catheter fracture with distal embolization is a rare complication in both adults and children and is usually associated with prolonged use and catheter fatigue. Retrieval of the embolized fragment should always be attempted to prevent possible complications. Awareness of this potential complication is important to facilitate diagnosis and management.
Predicting Outcomes after Minimally Percutaneous Nephrolithotomy with the Aid of a Patented System by Using the Guy's Stone Score
Authors: Deng Xiaolin , Song Leming , Xie Donghua , Huang Jianrong , Zhu Lunfeng , Wang Xiaolin , Fan Difu , Peng Zuofeng , Hu Min , Yang Zhongsheng , Liu Tairong , Ye Zhangqun
Published: February 2016

Objectives: At present, there is no report on the application of Guy's stone (GS) score in minimally invasive percutaneous nephrolithotomy (MPCNL). We therefore investigate the clinical effect of MPCNL by using a patented irrigation and clearance system according to the GS. Methods: A total of 222 consecutive patients were divided into 2 groups that were treated with MPCNL using the patented system or standard PCNL using Electro Medical System (EMS) ultrasound/ballistic trajectory lithotripsy and clearance system, respectively (124 patients in patented system group, 98 patients in EMS system group). The stone complexity and severity of complications were stratified by GS and Modified Clavien grading system in this study, respectively. The success and complication rates between MPCNL and PCNL were compared. Results: The patented system group had a significantly higher success rate (GS3: 95 vs. 43% and GS4: 67 vs. 31%) and a significantly less complications rate (GS3: 12 vs. 27% and GS4: 21 vs. 46%) in GS3 and GS4 compared with the EMS system group. Also, the patented system had significant lower complication rates in Clavien grades II-IV than that of the EMS system. Conclusion: The MPCNL using the patented irrigation and clearance system was more efficient in dealing with renal stones of high complexity (GS3-4).
Roles of Caveolin-1 in Angiotensin II–Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles
Authors: Umesalma Shaikamjad , Houwen Frederick Keith , Baumbach Gary L. , Chan Siu-Lung
Published: February 2016

Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II–mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II–mediated structural changes in pial arterioles. Cav-1–deficient (Cav-1
−/−
), MMP9-deficient (MMP9
−/−
), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6–8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II–induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1
−/−
mice. Ang II–induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1
−/−
mice. Ang II–mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9
−/−
mice. In conclusion, Cav-1 is essential in Ang II–mediated inward remodeling and hypertrophy in pial arterioles. Cav-1–induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II–mediated hypertrophy.
Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension
Authors: Spradley Frank T. , Tan Adelene Y. , Joo Woo S. , Daniels Garrett , Kussie Paul , Karumanchi S. Ananth , Granger Joey P.
Published: February 2016

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia.
Evidence to Maintain the Systolic Blood Pressure Treatment Threshold at 140 mm Hg for Stroke Prevention
Authors: Dong Chuanhui , Della-Morte David , Rundek Tatjana , Wright Clinton B. , Elkind Mitchell S.V. , Sacco Ralph L.
Published: February 2016

In 2014, the Eighth Joint National Committee revised the target maximum systolic blood pressure (SBP) from 140 to 150 mm Hg in patients aged ≥60 years without diabetes mellitus or chronic kidney disease. The evidence from cohort studies supporting this change was sparse, particularly among US minority populations. In the Northern Manhattan Study, 1750 participants aged ≥60 years and free of stroke, diabetes mellitus, and chronic kidney disease had SBP measured at baseline and were annually followed up for incident stroke. Mean age at baseline was 72±8 years, 63% were women, 48% Hispanic, 25% non-Hispanic white, and 25% non-Hispanic black. Among all participants, 40% were on antihypertensive medications; 43% had SBP <140 mm Hg, 20% had 140 to 149 mm Hg, and 37% had ≥150 mm Hg. Over a median follow-up of 13 years, 182 participants developed stroke. The crude stroke incidence was greater among individuals with SBP≥150 mm Hg (10.8 per 1000 person-years) and SBP 140 to 149 (12.3) than among those with SBP<140 (6.2). After adjusting for demographics, vascular risk factors, diastolic BP, and medication use, participants with SBP 140 to 149 mm Hg had an increased risk of stroke (hazard ratio, 1.7; 95% confidence interval, 1.2–2.6) compared with those with SBP <140 mm Hg. The increased stroke risk was most notable among Hispanics and non-Hispanic blacks. Raising the SBP threshold from 140 to 150 mm Hg as a new target for hypertension treatment in older individuals without diabetes mellitus or chronic kidney disease could have a detrimental effect on stroke risk reduction, especially among minority US populations.
Dopamine Modulation of Intertemporal Decision-making: Evidence from Parkinson Disease
Authors: Foerde Karin , Figner Bernd , Doll Bradley B. , Woyke Isabel C. , Braun Erin Kendall , Weber Elke U. , Shohamy Daphna
Published: February 2016

Choosing between smaller prompt rewards and larger later rewards is a common choice problem, and studies widely agree that frontostriatal circuits heavily innervated by dopamine are centrally involved. Understanding how dopamine modulates intertemporal choice has important implications for neurobiological models and for understanding the mechanisms underlying maladaptive decision-making. However, the specific role of dopamine in intertemporal decisions is not well understood. Dopamine may play a role in multiple aspects of intertemporal choices—the valuation of choice outcomes and sensitivity to reward delays. To assess the role of dopamine in intertemporal decisions, we tested Parkinson disease patients who suffer from dopamine depletion in the striatum, in either high (on medication, PDON) or low (off medication, PDOFF) dopaminergic states. Compared with both PDOFF and healthy controls, PDON made more farsighted choices and reduced their valuations less as a function of increasing time to reward. Furthermore, reduced discounting in the high dopaminergic state was robust across multiple measures, providing new evidence for dopamine's role in making decisions about the future.
Multivoxel Object Representations in Adult Human Visual Cortex Are Flexible: An Associative Learning Study
Authors: Senoussi Mehdi , Berry Isabelle , VanRullen Rufin , Reddy Leila
Published: February 2016

Learning associations between co-occurring events enables us to extract structure from our environment. Medial-temporal lobe structures are critical for associative learning. However, the role of the ventral visual pathway (VVP) in associative learning is not clear. Do multivoxel object representations in the VVP reflect newly formed associations? We show that VVP multivoxel representations become more similar to each other after human participants learn arbitrary new associations between pairs of unrelated objects (faces, houses, cars, chairs). Participants were scanned before and after 15 days of associative learning. To evaluate how object representations changed, a classifier was trained on discriminating two nonassociated categories (e.g., faces/houses) and tested on discriminating their paired associates (e.g., cars/chairs). Because the associations were arbitrary and counterbalanced across participants, there was initially no particular reason for this cross-classification decision to tend toward either alternative. Nonetheless, after learning, cross-classification performance increased in the VVP (but not hippocampus), on average by 3.3%, with some voxels showing increases of up to 10%. For example, a chair multivoxel representation that initially resembled neither face nor house representations was, after learning, classified as more similar to that of faces for participants who associated chairs with faces and to that of houses for participants who associated chairs with houses. Additionally, learning produced long-lasting perceptual consequences. In a behavioral priming experiment performed several months later, the change in cross-classification performance was correlated with the degree of priming. Thus, VVP multivoxel representations are not static but become more similar to each other after associative learning.
Chinoiseries for the Qing: A French Gift of Tapestries to the Qianlong Emperor
Authors: Smentek Kristel
Published: February 2016

In 1766 a set of chinoiserie tapestries produced by the Beauvais manufactory was presented to the Qianlong emperor on behalf of the French administration. Chinoiserie has conventionally been understood as a frivolous or superficial European response to China’s material culture; viewed from this perspective, the tapestries would seem to be a most unsuitable gift for the emperor. Yet Qianlong not only received the hangings, but he had a European-style palace built to house them. This article examines the circumstances surrounding the French offering, the Chinese priests who brought the gift from France to Beijing, and the meanings the tapestries could communicate in a diplomatic context marked not by official contact between the French and the Qing, but through an informal diplomacy negotiated through objects.
Ethnography and Empire through an Envoy’s Eye: The Manchu Official Akedun’s (1685-1756) Diplomatic Journeys to Chosǒn Korea
Authors: Liu Lihong
Published: February 2016

Akedun’s 1725 album Fengshi tu [Diplomatic Paintings] is an extraordinary example of the diplomatic painting genre popular during the High Qing era (1661-1796) that represents imperial delegations through the commissioners’ eye-witness experiences. Created after his four journeys to Chosǒn Korea, this album constructs a narrative in which Akedun carries out the role of an imperial ambassador while it captures ethnographic details of the lived places, curious customs, and courteous peoples of Korea. By rendering an imperial image of the Manchu Qing court, the album commemorates the amelioration of the Qing-Chosǒn relations after they had fraught confrontations during the Manchu’s post-conquest period. I argue that the Manchu ambassador Akedun keenly established his persona as an orthodox Confucian scholar in order to justify his position as a civil court-official whose missions were to negotiate for a mutual respect between the two regimes in the process of reaffirming an overarching Qing imperial order.
Evolutionary conservation of the circadian gene timeout in Metazoa
Authors: Li Diyan , Su Yuan , Tu Jianbo , Wei Ranlei , Fan Xiaolan , Yin Huadong , Hu Yaodong , Xu Huailiang , Yao Yongfang , Yang Deying , Yang Mingyao
Published: February 2016

Timeless (Tim) is considered to function as an essential circadian clock gene in Drosophila. Putative homologues of the Drosophila timeless gene have been identified in both mice and humans. While Drosophila contains two paralogs, timeless and timeout, acting in clock/light entrainment and chromosome integrity/photoreception, respectively, mammals contain only one Tim homolog. In this paper, we study the phylogeny of the timeless/timeout family in 48 species [including 1 protozoan (Guillardia theta), 1 nematode (Caenorhabditis elegans), 8 arthropods and 38 chordates], for which whole genome data are available by using MEGA (Molecular Evolutionary Genetics Analysis). Phylogenetic Analysis by Maximum Likelihood (PAML) was used to analyze the selective pressure acting on metazoan timeless/timeout genes. Our phylogeny clearly separates insect timeless and timeout lineages and shows that non-insect animal Tim genes are homologs of insect timeout. In this study, we explored the relatively rapidly evolving timeless lineage that was apparently lost from most deuterostomes, including chordates, and from Caenorhabditis elegans. In contrast, we found that the timeout protein, often confusingly called “timeless” in the vertebrate literature, is present throughout the available animal genomes. Selection results showed that timeout is under weaker negative selection than timeless. Finally, our phylogeny of timeless/timeout showed an evolutionary conservation of the circadian clock gene timeout in Metazoa. This conservation is in line with its multifunctionality, being essential for embryonic development and maintenance of chromosome integrity, among others.
Activity pattern of puma (Puma concolor) and its main prey in central Mexico
Authors: Soria-Díaz Leroy , Monroy-Vilchis Octavio , Zarco-González Zuleyma
Published: February 2016

Predator–prey dynamics are primarily determined by the predator’s ability to hunt and the prey’s strategies to avoid it. This dynamic can be influenced by ecological, environmental or anthropogenic factors. We analyzed the activity pattern of puma (Puma concolor) and its main prey species, armadillo (Dasypus novemcinctus), coati (Nasua narica) and white-tailed deer (Odocoileus virginianus) by means of photographic records. The pattern of activity of the predator species is not distributed uniformly throughout the day. No dependence of the activity pattern of the species on the moon phase was found. In addition, a statistically significant relationship between the activity pattern of puma and its main prey (armadillo) was obtained.
Allopatric speciation in the flightless Phoberus capensis (Coleoptera: Trogidae) group, with description of two new species
Authors: Strümpher Werner P. , Sole Catherine L. , Villet Martin H. , Scholtz Clarke H.
Published: February 2016

The namePhoberus capensis(Scholtz) is applied to a small flightless, keratinophagous beetle endemic to the Cape Floristic Region of South Africa. Its gross distribution stretches from roughly 1000 km from the Cederberg (32°24’22” S, 19°04’50” E) to Grahamstown (33°20’07” S, 26°32’50” E). The populations are spatially discrete, restricted to relict forests of the southern Cape and disjunct high montane refugia of the Cape Fold Mountains. We test the hypothesis that there is more than one distinct species nested within the nameP.capensis. Phylogenetic relationships among populations were inferred using molecular sequence data. The results support three distinct evolutionary lineages, which were also supported by morphological characters. Divergence time estimates suggest Pliocene-Pleistocene diversification. Based on these results, it is suggested that theP.capensislineage experienced climatically-driven allopatric speciation with sheltered Afrotemperate forests and high mountain peaks serving as important refugia in response to climatic ameliorations. TheP. capensiscomplex thus represents a speciation process in which flight-restricted populations evolved in close allopatry, possibly as recently as the Pleistocene. Two divergent and geographically distinct lineages are described as novel species: The new species,P.disjunctussp. n. andP.herminaesp. n., are illustrated by photographs of habitus and male aedeagi.
The Amphipoda of Sea City, Kuwait.—The Senticaudata (Crustacea)
Authors: MYERS ALAN A. , NITHYANANDAN MANICKAM
Published: February 2016

Thirteen species of Amphipoda Senticaudata were collected in Sea City, Kuwait using a Van Veen grab and an Ocklemann sledge. Of these seven species were new to science and are described and figured in this contribution.
Eriomacrotergum flechtmanni n. gen. n. sp. (Trombidiformes: Eriophyidae), a new eriophyoid mite from the cupuaçu tree, Theobroma grandiflorum, from northern Brazil
Authors: RODRIGUES DANIELA F.S. , NAVIA DENISE , OLIVEIRA ANIBAL R. , FERRAGUT FRANCISCO
Published: February 2016

A new eriophyid genus and species, tentatively placed in the Tegonotini, namely Eriomacrotergum flechtmanni n. gen. n. sp., is described from the Amazonian fruit tree cupuaçu Theobroma grandiflorum (Willd. Ex Spreng.) K. Schum. (Malvaceae), collected in northern Brazil. The new taxon presents a peculiar morphology in having a large opisthosomal plate and a very reduced prodorsal shield, with ocellar-like structures and scapular setae displaced laterally. Discussion on the most remarkable taxonomic traits is presented as well as similarities of the new genus with other Eriophyidae genera.
Review of morphometric measurements used in anuran species descriptions and recommendations for a standardized approach
Authors: WATTERS JESSA L. , CUMMINGS SEAN T. , FLANAGAN RACHEL L. , SILER CAMERON D.
Published: February 2016

Standardization and repeatability is at the heart of all scientific research, yet very little literature exists to standardize morphometric measurements within vertebrate groups. This is particularly true for amphibians. Our study attempts to rectify this lack of methodological standardization for the measurement of morphological characters in anurans through an extensive literature survey of 136 species descriptions representing 45 currently recognized families of frogs. The survey revealed 42 morphological measurements represented in five percent or more of the literature reviewed. All measurements are listed by most commonly used name, acronym, and most precise definition, and we provide statistics summarizing the variation in measurement use and description from the surveyed literature. Of these 42 measurements, a subset of 16 were found in the top 75% of all surveyed descriptions and identified as a focal set of recommended measurements in an effort to standardize the morphometric measurements that describe anuran species diversity. Illustrations of these 16 measurements are provided as a visual reference for standardizing their measurement.