bluuebunny/crossref_metadata_2025 huggingface dataset:
Prominin-1/CD133 expression as potential tissue-resident vascular endothelial progenitor cells in the pulmonary circulation
Authors: Sekine Ayumi , Nishiwaki Tetsu , Nishimura Rintaro , Kawasaki Takeshi , Urushibara Takashi , Suda Rika , Suzuki Toshio , Takayanagi Shin , Terada Jiro , Sakao Seiichiro , Tada Yuji , Iwama Atsushi , Tatsumi Koichiro
Published: April 2016

Pulmonary vascular endothelial cells could contribute to maintain homeostasis in adult lung vasculature. “Tissue-resident” endothelial progenitor cells (EPCs) play pivotal roles in postnatal vasculogenesis, vascular repair, and tissue regeneration; however, their local pulmonary counterparts remain to be defined. To determine whether prominin-1/CD133 expression can be a marker of tissue-resident vascular EPCs in the pulmonary circulation, we examined the origin and characteristics of prominin-1/CD133-positive (Prom1+) PVECs considering cell cycle status, viability, histological distribution, and association with pulmonary vascular remodeling. Prom1+PVECs exhibited high steady-state transit through the cell cycle compared with Prom1−PVECs and exhibited homeostatic cell division as assessed using the label dilution method and mice expressing green fluorescent protein. In addition, Prom1+PVECs showed more marked expression of putative EPC markers and drug resistance genes as well as highly increased activation of aldehyde dehydrogenase compared with Prom1−PVECs. Bone marrow reconstitution demonstrated that tissue-resident cells were the source of >98% of Prom1+PVECs. Immunofluorescence analyses revealed that Prom1+PVECs preferentially resided in the arterial vasculature, including the resistant vessels of the lung. The number of Prom1+PVECs was higher in developing postnatal lungs. Sorted Prom1+PVECs gave rise to colonies and formed fine vascular networks compared with Prom1−PVECs. Moreover, Prom1+PVECs increased in the monocrotaline and the Su-5416 + hypoxia experimental models of pulmonary vascular remodeling. Our findings indicated that Prom1+PVECs exhibited the phenotype of tissue-resident EPCs. The unique biological characteristics of Prom1+PVECs predominantly contribute to neovasculogenesis and maintenance of homeostasis in pulmonary vascular tissues.
Temporal Trends in Colorectal Cancer Screening among Asian Americans
Authors: Fedewa Stacey A. , Sauer Ann Goding , Siegel Rebecca L. , Smith Robert A. , Torre Lindsey A. , Jemal Ahmedin
Published: April 2016

Asian Americans (AA) are less likely to be screened for colorectal cancer compared with non-Hispanic Whites (NHW), with a widening disparity for some AA subgroups in the early 2000s. Whether these patterns have continued in more recent years is unknown. We examined temporal trends in colorectal cancer screening among AA overall compared with NHWs and by AA subgroup (Chinese, Japanese, Korean, Filipino, South Asian, Vietnamese) using data from the 2003, 2005, 2007, and 2009 California Health Interview Surveys. Unadjusted (PR) and adjusted (aPR) prevalence ratios for colorectal cancer screening, accounting for sociodemographic, health care, and acculturation factors, were calculated for respondents ages 50 to 75 years (NHW n = 60,125; AA n = 6,630). Between 2003 and 2009, colorectal cancer screening prevalence increased from 43.3% to 64.6% in AA (P ≤ 0.001) and from 58.1% to 71.4% in NHW (P ≤ 0.001). Unadjusted colorectal cancer screening was significantly lower among AA compared with NHW in 2003 [PR = 0.74; 95% confidence interval (CI), 0.68–0.82], 2005 (PR = 0.78; 95% CI, 0.72–0.84), 2007 (PR = 0.91; 95% CI, 0.85–0.96), and 2009 (PR = 0.90; 95% CI, 0.84–0.97), though disparities narrowed over time. After adjustment, there were no significant differences in colorectal cancer screening between the two groups, except in 2003. In subgroup analyses, between 2003 and 2009, colorectal cancer screening significantly increased by 22% in Japanese, 56% in Chinese, 47% in Filipino, and 94% in Koreans. In our study of California residents, colorectal cancer screening disparities between AA and NHW narrowed, but were not eliminated and screening prevalence among AA remains below nationwide goals, including the Healthy People 2020 goal of increasing colorectal cancer screening prevalence to 70.5%. Cancer Epidemiol Biomarkers Prev; 25(6); 995–1000. ©2016 AACR.
A Quantitative Analysis of Subclonal and Clonal Gene Mutations before and after Therapy in Chronic Lymphocytic Leukemia
Authors: Amin Nisar A. , Seymour Erlene , Saiya-Cork Kamlai , Parkin Brian , Shedden Kerby , Malek Sami N.
Published: April 2016

Purpose: Chronic lymphocytic leukemia (CLL)-associated gene mutations that influence CLL cell fitness and chemotherapy resistance should increase in clonal representation when measured before therapy and at relapse.

Experimental Design: To uncover mutations associated with CLL relapse, we have performed whole-exome sequencing in a discovery cohort of 61 relapsed CLL patients identifying 86 recurrently mutated genes. The variant allele fractions (VAF) of 19 genes with mutations in ≥3 of 61 cases were measured in 53 paired pre- and posttreatment CLL samples sorted to purity using panel-based deep resequencing or by droplet digital PCR.

Results: We identify mutations in TP53 as the dominant subclonal gene driver of relapsed CLL often demonstrating substantial increases in VAFs. Subclonal mutations in SAMHD1 also recurrently demonstrated increased VAFs at relapse. Mutations in ATP10A, FAT3, FAM50A, and MGA, although infrequent, demonstrated enrichment in ≥2 cases each. In contrast, mutations in NOTCH1, SF3B1, POT1, FBXW7, MYD88, NXF1, XPO1, ZMYM3, or CHD2 were predominantly already clonal prior to therapy indicative of a pretreatment pathogenetic driver role in CLL. Quantitative analyses of clonal dynamics uncover rising, stable, and falling clones and subclones without clear evidence that gene mutations other than in TP53 and possibly SAMHD1 are frequently selected for at CLL relapse.

Conclusions: Data in aggregate support a provisional categorization of CLL-associated recurrently mutated genes into three classes (i) often subclonal before therapy and strongly enriched after therapy, or, (ii) mostly clonal before therapy or without further enrichments at relapse, or, (iii) subclonal before and after therapy and enriching only in sporadic cases. Clin Cancer Res; 22(17); 4525–35. ©2016 AACR.
DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China
Authors: Li Xin , Cui Yingying , Sun Zhenchang , Zhang Lei , Li Ling , Wang Xinhua , Wu Jingjing , Fu Xiaorui , Ma Wang , Zhang Xudong , Chang Yu , Nan Feifei , Li Wencai , Su Liping , Wang Jinghua , Xue Hongwei , Zhang Mingzhi
Published: April 2016

Purpose: Optimal treatment strategies for advanced natural killer/T (NK/T)-cell lymphoma have not been fully defined. We compared the safety and efficacy of DDGP and SMILE regimens for advanced NK/T-cell lymphoma in a randomized controlled, multicenter, and open-label clinical trial.

Experimental Design: Patients were newly diagnosed in stages III–IV and had performance scores in 0 to 2. Six cycles of DDGP (dexamethasone, cisplatin, gemcitabline, and pegaspargase) or SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy were randomly assigned to them. The primary end point was progression-free survival (PFS). Secondary end points included response rate and overall survival (OS). The trial is ongoing and is registered with ClinicalTrials.gov (No. NCT01501149).

Results: Of 42 patients enrolled, 21 were treated with DDGP therapy, and 21 patients were treated with SMILE therapy. The 1-year PFS and 2-year OS rates were better in the DDGP group than that in the SMILE group (86% vs. 38% for 1-year PFS, P = 0.006; 74% vs. 45% for 2-year OS, P = 0.027). Complete remission (CR) rate and overall response rate (ORR) of the DDGP group were higher than that in the SMILE group (71% vs. 29%, P = 0.005 for CR rate; 95% vs. 67%, P = 0.018 for ORR). The SMILE group showed more serious leucopenia (P = 0.030) and severe allergic reaction (P = 0.015) than the DDGP group. In addition, two cases in the SMILE group underwent grade 4 mucosal reaction.

Conclusions: DDGP chemotherapy resulted in significant improvement in PFS, OS, and better tolerability compared with SMILE chemotherapy for newly diagnosed advanced NK/T-cell lymphoma patients. Clin Cancer Res; 22(21); 5223–8. ©2016 AACR.
Targeting IκB Kinase β/NF-κB Signaling in Human Prostate Cancer by a Novel IκB Kinase β Inhibitor CmpdA
Authors: Zhang Yanting , Lapidus Rena G. , Liu Peiyan , Choi Eun Yong , Adediran Samusi , Hussain Arif , Wang Xinghuan , Liu Xuefeng , Dan Han C.
Published: April 2016

NF-κB plays an important role in many types of cancer, including prostate cancer, but the role of the upstream kinase of NF-κB, IKKβ, in prostate cancer has neither been fully documented nor are there any effective IKKβ inhibitors used in clinical settings. Here, we have shown that IKKβ activity is mediated by multiple kinases including IKKα in human prostate cancer cell lines that express activated IKKβ. IHC analysis (IHC) of human prostate cancer tissue microarrays (TMA) demonstrates that phosphorylation of IKKα/β within its activation loop gradually increases in low to higher stage tumors as compared with normal tissue. The expression of cell proliferation and survival markers (Ki-67, Survivin) and epithelial-to-mesenchymal transition (EMT) markers (Slug, Snail), as well as cancer stem cell (CSC)-related transcription factors (Nanog, Sox2, Oct-4), also increase in parallel among the respective TMA samples analyzed. IKKβ, but not NF-κB, is found to regulate Nanog, which, in turn, modulates the levels of Oct4, Sox2, Snail, and Slug, indicating an essential role of IKKβ in regulating CSCs and EMT. The novel IKKβ inhibitor CmpdA inhibits constitutively activated IKKβ/NF-κB signaling, leading to induction of apoptosis and inhibition of proliferation, migration, and stemness in these cells. CmpdA also significantly inhibits tumor growth in xenografts without causing apparent in vivo toxicity. Furthermore, CmpdA and docetaxel act synergistically to inhibit proliferation of prostate cancer cells. These results indicate that IKKβ plays a pivotal role in prostate cancer, and targeting IKKβ, including in combination with docetaxel, may be a potentially useful strategy for treating advanced prostate cancer. Mol Cancer Ther; 15(7); 1504–14. ©2016 AACR.
Clinical Impact of Bevacizumab in Patients with Relapsed Glioblastoma: Focus on a Real-Life Monocentric SurVey (SV1 Study)
Authors: Rivoirard Romain , Chargari Cyrus , Guy Jean-Baptiste , Nuti Christophe , Peoc''h Michel , Forest Fabien , Falk Alexander Tuan , Garin Clemence , Adjabi Anissa , Hoarau Delphine , Fotso Marie-Jeannette , Langrand Escure Julien , Moriceau Guillaume , Fournel Pierre , Boutet Claire , Magné Nicolas
Published: April 2016

Objectives: Glioblastoma is one of the most frequent primitive brain tumors. Patients who experience tumor relapse after surgery and concomitant radiochemotherapy have a dismal prognosis. The objective of this study is to analyze efficacy data in terms of overall survival (OS) and progression- free survival (PFS) following combination therapy with bevacizumab (BVZ) and irinotecan among patients with relapsed glioblastoma. Safety data will also be reviewed and all results will be compared with data of the literature. Methods: In this single-center retrospective study, all records of patients treated with BVZ and irinotecan for a relapsed glioblastoma were analyzed. Each chemotherapy cycle was repeated every 15 days until progression. Magnetic resonance imaging and neurologic examination were repeated every 6 weeks during treatment. Results: Forty-five patients were analyzed. The median number of BVZ-irinotecan cycles was 8 (range 1-38). Median PFS was 26 weeks and median OS was 28 weeks. Eighteen of the 45 patients (40% of cases) had an objective response 6 months after initiation of treatment. Two patients had to discontinue treatment due to toxicity. Conclusions: The results of the SV1 study are consistent with those found in phase II studies evaluating the same treatment. The irinotecan-BVZ combination is effective in relapsed glioblastoma with acceptable toxicity. Biomarkers predictive of response to BVZ should help in the selection of patients who could benefit from treatment.
Blood-Cerebrospinal Fluid Barrier Integrity in Delirium Determined by Q-Albumin
Authors: Hov Karen Roksund , Berg Jens Petter , Frihagen Frede , Ræder Johan , Hall Roanna , Wyller Torgeir Bruun , Watne Leiv Otto
Published: April 2016

Background/Aims: Delirium is a common and serious complication in hospitalised patients and its pathophysiology is incompletely understood. We aimed to examine whether blood-cerebrospinal fluid barrier dysfunction, as measured by Q-albumin (the ratio of cerebrospinal fluid albumin to serum albumin), was associated with delirium. Methods: In this prospective cohort study of hip fracture patients from Oslo University Hospital, Norway, serum was collected preoperatively and cerebrospinal fluid just before the onset of spinal anaesthesia. Albumin levels in serum and cerebrospinal fluid were analysed consecutively, and Q-albumin was calculated using the formula [cerebrospinal fluid albumin (mg/dl) × 1,000]/[serum albumin (mg/dl)]. Q-albumin >10.2 was used as the cut-off for blood-cerebrospinal fluid barrier dysfunction. Patients were assessed daily for delirium using the Confusion Assessment Method. Results: Out of 120 patients, 69 had delirium, 22 had subsyndromal delirium, and 29 were free from delirium. The majority of patients, i.e. 106 (88%), had intact blood-cerebrospinal fluid barrier integrity, but all 14 patients with blood-cerebrospinal barrier dysfunction had delirium (n = 11) or subsyndromal delirium (n = 3). Conclusions: The results suggest that blood-cerebrospinal fluid barrier dysfunction may be relevant for delirium pathophysiology when it occurs. However, the low prevalence (16% of delirium patients) indicates that this is not a prerequisite for the development of delirium.
Antibiotic Resistance Patterns and a Survey of Metallo-β-Lactamase Genes Including bla-IMP and bla-VIM Types in Acinetobacter baumannii Isolated from Hospital Patients in Tehran
Authors: Aghamiri Samira , Amirmozafari Nour , Fallah Mehrabadi Jalil , Fouladtan Babak , Hanafi Abdar Mojtaba
Published: April 2016

Background: Metallo-β-lactamases (MBLs) producing strains of Acinetobacter baumannii are serious etiological agents of hospital infections worldwide. Among the β- lactams, carbapenems are the most effective antibiotics used against A. baumannii. However, resistance to these drugs among clinical strains of A. baumannii has been increasing in recent years. In this study, the antimicrobial sensitivity patterns of A. baumannii strains isolated from eleven different hospitals in Tehran, Iran, and the prevalence of MBL genes (bla-VIM and bla-IMP) were determined. Method: During a period of 5 months, 176 isolates of A. baumannii were collected from different clinical specimens from hospitalized patients in Tehran. All isolates were confirmed by biochemical methods. The isolates were tested for antibiotic sensitivity by the Kirby-Bauer disk diffusion method. Following minimum inhibitory concentration determination, imipenem-resistant isolates were further tested for MBL production by the double disk synergy test (DDST) method. PCR assays were performed for the detection of the MBL genes bla-IMP and bla-VIM. Results: The DDST phenotypic method indicated that among the 169 imipenem-resistant isolates, 165 strains were MBL positive. The PCR assays revealed that 63 of the overall isolates (36%) carried the bla-VIM gene and 70 strains (40%) harbored bla-IMP. Conclusions: It is obvious that nosocomial infections associated with multidrug-resistant Acinetobacter spp. are on the rise. Therefore, the determination of antibiotic sensitivity patterns and screening for MBL production among A. baumannii isolates is important for controlling clinical Acinetobacter infections.
Direct Observation versus Endoscopic Video Recording-Based Rating with the Objective Structured Assessment of Technical Skills for Training of Laparoscopic Cholecystectomy
Authors: Nickel Felix , Hendrie Jonathan D. , Stock Christian , Salama Mohamed , Preukschas Anas A. , Senft Jonas D. , Kowalewski Karl F. , Wagner Martin , Kenngott Hannes G. , Linke Georg R. , Fischer Lars , Müller-Stich Beat P.
Published: April 2016

Purpose: The validated Objective Structured Assessment of Technical Skills (OSATS) score is used for evaluating laparoscopic surgical performance. It consists of two subscores, a Global Rating Scale (GRS) and a Specific Technical Skills (STS) scale. The OSATS has accepted construct validity for direct observation ratings by experts to discriminate between trainees' levels of experience. Expert time is scarce. Endoscopic video recordings would facilitate assessment with the OSATS. We aimed to compare video OSATS with direct OSATS. Methods: We included 79 participants with different levels of experience [58 medical students, 15 junior residents (novices), and 6 experts]. Performance of a cadaveric porcine laparoscopic cholecystectomy (LC) was evaluated with OSATS by blinded expert raters by direct observation and then as an endoscopic video recording. Operative time was recorded. Results: Direct OSATS rating and video OSATS rating correlated significantly (ρ = 0.33, p = 0.005). Significant construct validity was found for direct OSATS in distinguishing between students or novices and experts. Students and novices were not different in direct OSATS or video OSATS. Mean operative times varied for students (73.4 ± 9.0 min), novices (65.2 ± 22.3 min), and experts (46.8 ± 19.9 min). Internal consistency was high between the GRS and STS subscores for both direct and video OSATS with Cronbach's α of 0.76 and 0.86, respectively. Video OSATS and operative time in combination was a better predictor of direct OSATS than each single parameter. Conclusion: Direct OSATS rating was better than endoscopic video rating for differentiating between students or novices and experts for LC and should remain the standard approach for the discrimination of experience levels. However, in the absence of experts for direct rating, video OSATS supplemented with operative time should be used instead of single parameters for predicting direct OSATS scores.
Assessment of Arterial Stiffness Using the Cardio-Ankle Vascular Index
Authors: Miyoshi Toru , Ito Hiroshi
Published: April 2016

Background: Arterial stiffness is an independent predictor of outcomes for patients with cardiovascular disease. Although measurement of pulse wave velocity is a widely accepted, noninvasive approach for the assessment of arterial stiffness, its accuracy is affected by changes in blood pressure. Summary: The cardio-ankle vascular index (CAVI) is an index of the overall stiffness of the artery from the origin of the aorta to the ankle and is theoretically independent of blood pressure at the time of measurement. CAVI increases linearly with age and is elevated even in mild arteriosclerotic disease. It can identify differences in the degree of arteriosclerosis among patients with severe arteriosclerotic disease and better reflects the severity of disease of the coronary artery than does brachial-ankle pulse wave velocity. Patients with higher CAVI values show a poor prognosis compared with those with lower CAVI values. Furthermore, CAVI can be lowered by controlling diabetes mellitus and hypertension. Key Messages: The primary aims of assessing arterial stiffness using CAVI are to assist in the early detection of arteriosclerosis, allowing timely treatment and lifestyle modification, and to quantitatively evaluate the progression of disease and the effectiveness of treatment. Whether CAVI-guided therapy can improve prognosis in high-risk patients needs to be further examined to confirm the clinical usefulness of this measure.
Toll-Like Receptor 7-Targeted Therapy in Respiratory Disease
Authors: Lebold Katie M. , Jacoby David B. , Drake Matthew G.
Published: April 2016

Allergic asthma and allergic rhinitis are inflammatory diseases of the respiratory tract characterized by an excessive type-2 T helper cell (Th2) immune response. Toll-like receptor 7 (TLR7) is a single-stranded viral RNA receptor expressed in the airway that initiates a Th1 immune response and has garnered interest as a novel therapeutic target for treatment of allergic airway diseases. In animal models, synthetic TLR7 agonists reduce airway hyperreactivity, eosinophilic inflammation, and airway remodeling while decreasing Th2-associated cytokines. Furthermore, activation of TLR7 rapidly relaxes airway smooth muscle via production of nitric oxide. Thus, TLR7 has dual bronchodilator and anti-inflammatory effects. Two TLR7 ligands with promising pharmacologic profiles have entered clinical trials for the treatment of allergic rhinitis. Moreover, TLR7 agonists are potential antiviral therapies against respiratory viruses. TLR7 agonists enhance influenza vaccine efficacy and also reduce viral titers when given during an active airway infection. In this review, we examine the current data supporting TLR7 as a therapeutic target in allergic airway diseases.
Portinari's Drawings of Hans Staden: Oblivion and Memory of the Colonial Past
Authors: Villas Bôas Luciana
Published: April 2016

This article explores the production and transmission of illustrations Candido Portinari made for a North-American edition of Hans Staden's book on sixteenth-century Brazil. Made in 1941, the drawings fell into oblivion for almost sixty years, until their posthumous publication in 1998 in Brazil. The article argues that the destiny of the drawings is symptomatic for the articulation of the cultural memory of the colonial past in Brazil. Based upon the analysis of their critical reception and visual repertoire, it suggests that the drawings diverge from traditional representations of the death of indigenous people by challenging the temporality underlying the national framework of colonial memory
Introduction to “Parasitic Drama”. Mechanisms of theatricality in Elfriede Jelinek’s Die Kontrakte des Kaufmanns / The Merchant’s Contracts
Authors: Monteiro Bruno
Published: April 2016

In this paper, we present a critical exposition on the play Die Kontrakte des Kaufmanns, by Elfriede Jelinek, which aims to present the literary composition principles used by the writer in his proposition of a "parasitical drama". Concurrently, we will seek to retrieve the set of contextual references that precedes that dramatization. For this purpose, we will start by exposing the play's incubation context, then moving to the introduction of the author’s ironic and parodic approach on the market’s legitimization and naturalization mechanisms and its financial operations, in particular by econometric metaphysics and the media’s common sense. On a third point, we will present the specifically literary procedures by which the writer reveals the logic of the capitalist economy as a regime of bodies’ annihilation. Finally, we summarize the writer’s intention of using the theater as a viewers activation device by way of “horror”.
Analysis of a didactic sequence for German language teaching in Kindergarten
Authors: Queroz Josiete C. , Stutz Lidia
Published: April 2016

Though oral language is essential in our lives, since through it we express our feelings, thoughts, desires, experiences and build knowledge, little has been said about it in early childhood education. In this way, grounded on text genre theory, from the socio-discursive interactionist perspective (BRONCKART 2012; SCHNEUWLY/ DOLZ 2013), we developed a didactic sequence (DS) based on two animal tales. Through this interventionist proposal, we concentrate on improving teaching and learning in a private kindergarten in which the participants are 3 to 4 year-old children. For this article we aim at describing and evaluating the configuration of the DS as well as analyzing it in terms of language capacities. In addition, we present partial results of the children’s oral productions. Analyzing the DS, we found a prevalence of significance capacities (15%) and the linguistic-discursive capacities (12.5%). Our results show that the DS provides activities for children’s oral production, considering that the two chosen stories and the activities involve them emotionally, psychologically and cognitively. In addition to retell the story, students began using the vocabulary and even certain expressions in their daily lives
Selective Vascular Endothelial Protection Reduces Cardiac Dysfunction in Chronic Heart Failure
Authors: Maupoint Julie , Besnier Marie , Gomez Elodie , Bouhzam Najime , Henry Jean-Paul , Boyer Olivier , Nicol Lionel , Mulder Paul , Martinet Jérémie , Richard Vincent
Published: April 2016

Background—

Chronic heart failure (CHF) induces endothelial dysfunction in part because of decreased nitric oxide (NO
·
) production, but the direct link between endothelial dysfunction and aggravation of CHF is not directly established. We previously reported that increased NO production via inhibition of protein tyrosine phosphatase 1B (PTP1B) is associated with reduced cardiac dysfunction in CHF. Investigation of the role of endothelial PTP1B in these effects may provide direct evidence of the link between endothelial dysfunction and CHF.

Methods and Results—

Endothelial deletion of PTP1B was obtained by crossing LoxP-PTP1B with Tie2-Cre mice. CHF was assessed 4 months after myocardial infarction. In some experiments, to exclude gene extinction in hematopoietic cells, Tie2-Cre/LoxP-PTP1B mice were lethally irradiated and reconstituted with bone marrow from wild-type mice, to obtain mouse with endothelial-specific deletion of PTP1B. Vascular function evaluated ex vivo in mesenteric arteries showed that in wild-type mice, CHF markedly impaired NO-dependent flow-mediated dilatation. CHF-induced endothelial dysfunction was less marked in endoPTP1B
−/−
mice, suggesting restored NO production. Echocardiographic, hemodynamic, and histological evaluations demonstrated that the selectively improved endothelial function was associated with reduced left ventricular dysfunction and remodeling, as well as increased survival, in the absence of signs of stimulated angiogenesis or increased cardiac perfusion.

Conclusions—

Prevention of endothelial dysfunction, by endothelial PTP1B deficiency, is sufficient to reduce cardiac dysfunction post myocardial infarction. Our results provide for the first time a direct demonstration that endothelial protection per se reduces CHF and further suggest a causal role for endothelial dysfunction in CHF development.
Long-Term Clinical Outcomes After Bioresorbable Vascular Scaffold Implantation for the Treatment of Coronary In-Stent Restenosis
Authors: Moscarella Elisabetta , Ielasi Alfonso , Granata Francesco , Coscarelli Sebastian , Stabile Eugenio , Latib Azeem , Cortese Bernardo , Tespili Maurizio , Tanaka Akihito , Capozzolo Claudia , Caliendo Luigi , Colombo Antonio , Varricchio Attilio
Published: April 2016

Background—

Treatment of in-stent restenosis (ISR) is still challenging. In this setting, the use of bioresorbable vascular scaffold (BVS) seems attractive because it allows drug delivery combined with transient vessel scaffolding. We aimed to investigate the long-term results after BVS use in ISR lesions.

Methods and Results—

A prospective analysis was performed on all patients who underwent percutaneous coronary intervention with BVS implantation for ISR at 7 Italian Centers. Primary end point was the device-oriented composite end point (cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) at the longest follow-up available. From April 2012 to June 2014, 116 patients (127 lesions) underwent percutaneous coronary intervention for ISR with BVS implantation. Among the ISR lesions, the majority were drug-eluting stent ISR (78, 61.6%), de novo ISR (92, 72.4%), and diffuse ISR (81, 63.8%). Procedural success was achieved for all (100%) patients. No in-hospital death, myocardial infarction, or revascularization occurred. At 15 months of follow-up, the incidence of the device-oriented composite end point estimated with the Kaplan–Meier method was 9.1%. No significant differences were reported between drug-eluting stent and bare-metal stent ISR groups in terms of device-oriented composite end point (10.9% versus 6.4%; hazard ratio, 1.7; 95% confidence interval, 0.5–6.5;
P
=0.425) and its singular components (cardiac death: 2.8% versus 2.0%, hazard ratio, 1.3; 95% confidence interval, 0.1–14.1,
P
=0.843; target vessel myocardial infarction: 1.5% versus 0%,
P
=0.421; ischemia-driven target lesion revascularization: 9.6% versus 4.4%, hazard ratio, 2.3; 95% confidence interval, 0.5–10.8,
P
=0.309).

Conclusions—

Our registry suggests that the use of BVS implantation for the treatment of complex drug-eluting stent and bare-metal stent ISR lesions might be associated with acceptable long-term clinical outcomes.
Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure
Authors: Sun Haipeng , Olson Kristine C. , Gao Chen , Prosdocimo Domenick A. , Zhou Meiyi , Wang Zhihua , Jeyaraj Darwin , Youn Ji-Youn , Ren Shuxun , Liu Yunxia , Rau Christoph D. , Shah Svati , Ilkayeva Olga , Gui Wen-Jun , William Noelle S. , Wynn R. Max , Newgard Christopher B. , Cai Hua , Xiao Xinshu , Chuang David T. , Schulze Paul Christian , Lynch Christopher , Jain Mukesh K. , Wang Yibin
Published: April 2016

Background—

Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudied.

Methods and Results—

Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key upstream regulator of the BCAA catabolic regulation in the heart. Studies using a genetic mouse model revealed that BCAA catabolic defect promoted heart failure associated with induced oxidative stress and metabolic disturbance in response to mechanical overload. Mechanistically, elevated branched-chain α-keto acids directly suppressed respiration and induced superoxide production in isolated mitochondria. Finally, pharmacological enhancement of branched-chain α-keto acid dehydrogenase activity significantly blunted cardiac dysfunction after pressure overload.

Conclusions—

BCAA catabolic defect is a metabolic hallmark of failing heart resulting from Krüppel-like factor 15–mediated transcriptional reprogramming. BCAA catabolic defect imposes a previously unappreciated significant contribution to heart failure.
Tragedy in the Crosshairs of the Present
Authors: Holmes Brooke
Published: April 2016

A number of developments in the study of Greek literature over the past few decades have broken down boundaries of canon and genre, opening up a wide range of texts once deemed degenerate or unavailable to literary analysis, expanding the networks within which literary texts are interpreted, and bringing renewed attention to the reception of ancient texts in later periods up to the present. The rise of reception studies, in particular, raises new questions about how our own position within specific present moments not only imposes constraints on the interpretation of ancient texts but also enables it. In this essay, I survey these developments using Greek tragedy, the most canonical of genres, as a case study. I argue that we need to develop strategies of interpretation more attuned to resonances between contemporary quandaries and our extant tragedies while remaining committed to forms of social and historical difference. I pay particular attention to the problems of agency that tragedy raises at the juncture of the human and the nonhuman worlds.
Philosophy & Its Classical Past
Authors: Mitsis Phillip
Published: April 2016

The notion that philosophers can abandon their history and set their arguments on new foundations has a long history. One strain of recent philosophy that traces its roots to Frege has been particularly confident in this regard, and its rejection of a classical past has had widespread influences on the study of ancient philosophy over the past several decades. With the waning of this recent paradigm, however, the possibility of philosophical engagement between the old and new has again led to significant work in several areas of philosophy. I concentrate on one of these, the philosophy of death, and also ask whether ancient philosophy might furnish models that enable contemporary philosophers to rise above their specialisms and address crucial issues in a public discourse, allowing for both mutual intelligibility and criticism.
The Environmental Fall of the Roman Empire
Authors: Harper Kyle
Published: April 2016

Global environmental history is currently being enriched by troves of new data, and new models of environmental variability and human impact. Earth scientists are rapidly expanding historians’ knowledge of the paleoclimate through the recovery and analysis of climate proxies such as ice cores, tree rings, stalagmites, and marine and lake sediments. Further, archaeologists and anthropologists are using novel techniques and methods to study the history of health and disease, as revealed through examination of bones and paleomolecular evidence. These possibilities open the way for historians to participate in a conversation about the long history of environmental change and human response. This essay considers how one of the most classic of all historical questions–the fall of the Roman Empire–can receive an answer enriched by new knowledge about the role of environmental change.
What is Ancient History?
Authors: Morris Ian , Scheidel Walter
Published: April 2016

Every society has told stories about ancient times, but contemporary ancient history was the product of two main developments. The first was the invention of writing, which made scholarly study of the past possible, and the second was the explosion of knowledge about the world from the eighteenth century onward. Europeans responded to this explosion by inventing two main versions of antiquity: the first, an evolutionary model, was global and went back to the origins of humanity; and the second, a classical model, treated Greece and Rome as turning points in world history. These two views of antiquity have competed for two hundred and fifty years, but in the twenty-first century, the evidence and methods available to ancient historians are changing faster than at any other time since the debate began. We should therefore expect the balance between the two theories to shift dramatically. We close by considering some possible areas of engagement.
Introduction
Authors: Moorjani Angela , de Ruyter Danièle
Published: April 2016

When a quarter of a century had passed since Beckett drew his last breath, we thought of the many scholars, translators, artists, writers, theatre and media practitioners who had worked with him or met with him now many years ago to muse over his work. What traces of their encounters, we wondered, were still filed away in personal archives waiting to be shared?
Reminiscences of a Late Friendship
Authors: Rodríguez-Gago Antonia
Published: April 2016

I have never written about my friendship with Samuel Beckett. If I do so now, it is to convey the great respect and extreme generosity he showed people who dedicated much of their creative lives to his work. Corresponding with Beckett from 1982 to 1989 and meeting him during the last four years of his life was a privilege and a fascinating experience.
The Many-Body Problem
Authors: Moorjani Kishin
Published: April 2016

This conversation touches on Beckett’s interest in mathematics and science and probes their underlying connections to art and literature.
“For the usual, at the usual”
Authors: Dukes Gerry
Published: April 2016

A brief memoir of meetings with Beckett from 1986 to 1989 at three locations all in the same area of Paris and indications of the subjects that came up for discussion.
Rencontre avec Samuel Beckett
Authors: Kamyabi Mask Ahmad
Published: April 2016

J’ attendais Beckett dans le hall de l’ hôtel quand un homme entra par la porte du café, me dépassa et s’ arrêta au milieu du hall, c’ était le 8 septembre 1988. Il semblait chercher quelqu’ un et, au moment où il se tourna vers moi, je reçus la confirmation de l’ impression que j’ avais eue : c’ était bien lui ! Il m’ invita à l’ accompagner au café. J’ étais assez angoissé à l’ idée de l’ interview qui se préparait car je voulais essayer de le faire parler de son œuvre et plus particulièrement de ses pièces et de leur mise en scène.
“Come back soon!”
Authors: Madden le Brocquy Anne
Published: April 2016

Irish artist Anne Madden recalls her and her painter husband Louis le Brocquy’s eleven years of friendship with Samuel Beckett at the end of his life. She recollects their many conversations and Le Brocquy’s painted images of the writer, his illustrations for Beckett’s last piece of fiction, and the costumes and set he conceived and painted for a production of Waiting for Godot at Dublin’s Gate Theatre.
Bothering Him with My Questions …
Authors: Kędzierski Marek
Published: April 2016

Recollections of meetings with Beckett from the first in 1980 trying to convince him to direct Endgame in Cracow and conversations, ranging widely over the next few years on translating, directing, and adapting his works.
Un après-midi avec Samuel Beckett
Authors: Kamel Nadia
Published: April 2016

En 1968 je préparais une thèse de doctorat à Cairo sur le personnage dans l’ œuvre romanesque de Samuel Beckett. Je dois reconnaître que j’ ai été parmi ‘les heureux’ qui ont pu le rencontrer, lui parler, correspondre avec lui, et recevoir ses livres dédicacés. Arrivée à Paris le 8 juin 1969, je m’ empresse d’ aller repérer le 38 boulevard Saint-Jacques afin de bien connaître l’ adresse, pour ne pas me tromper ou perdre du temps à chercher. Le jour suivant à dix-huit heures précises, je sonne à sa porte et me voilà devant Samuel Beckett …
Czy batik jest symbolem tożsamości narodowej w Indonezji? Narodziny i rozwój indonezyjskiego stroju narodowego
Authors: Wacławek Joanna Ilona
Published: April 2016

Is batik a symbol of the national identity in Indonesia? The birth and the transfiguration of Indonesian national costume This study investigates the national costume in Indonesia, especially one of its components – batik. Is batik a symbol of Indonesian national identity, or is it just a proof of domination of the Javanese culture? In this article, I explore the ways in which batik became a popular costume for Indonesian citizens, defined also as a vehicle for manifestations of many different ideas and identities. I analyze not only briefly a history of batik as a part of Indonesian national costume, but also the ways of its understanding, both in the past an in contemporary Indonesia. Czy batik jest symbolem tożsamości narodowej w Indonezji? Narodziny i rozwój indonezyjskiego stroju narodowegoPrzedmiotem analizy w niniejszej pracy jest indonezyjski strój narodowy, zwłaszcza jeden z jego elementów – batik. Czy batik jest symbolem tożsamości narodowej w Indonezji, czy jedynie stanowi dowód na dominację kultury jawajskiej? W artykule omawiam ścieżki transformacji batiku w ubiór, bądź część ubioru, noszony przez Indonezyjczyków, definiowany zarazem jako przestrzeń służąca manifestowaniu rozmaitych poglądów, przekonań i tożsamości. Badam nie tylko historię batiku jako elementu narodowego stroju w Indonezji, lecz także sposoby jego odczytywania, zarówno w przeszłości, jak i obecnie.
Determinants of Chronic Total Occlusion in Patients With Peripheral Arterial Occlusive Disease
Authors: Hamur Hikmet , Onk Oruc Alper , Vuruskan Ertan , Duman Hakan , Bakirci Eftal Murat , Kucuksu Zafer , Degirmenci Husnu , Buyuklu Mutlu , Topal Ergun
Published: April 2016

Chronic total occlusion (CTO) is a common finding in 40% of the patients with peripheral arterial disease (PAD). The aim of this study was to investigate the determinants of CTO in patients with PAD. The study included a total of 211 nonanemic patients with PAD. All patients were categorized according to the Fontaine classification. In lower extremity angiography cohorts, CTO− patients were designated as group 1 and CTO+ patients were designated as group 2. Patients with CTO had significantly higher red cell distribution width (RDW), neutrophil–lymphocyte ratio, uric acid, and high-sensitivity C-reactive protein compared to patients without CTO ( P ≤ .001, P = .036, P ≤ .001, and P = .015, respectively). Albumin, total bilirubin, and direct bilirubin were significantly lower in the patients with CTO compared to patients without CTO ( P = .023, P ≤ .001, and P = .049, respectively). Multivariate logistic regression analysis showed that RDW, uric acid, and total bilirubin were independent predictors of CTO in patients with PAD. We demonstrated that increased RDW and uric acid levels and lower total bilirubin values were independently associated with CTO in patients with PAD.
Portable Deep-Ultraviolet (DUV) Raman for Standoff Detection
Authors: Hopkins Adam J. , Cooper Justin L. , Profeta Luisa T.M. , Ford Alan R.
Published: April 2016

Alakai Defense Systems has recently developed a man-portable ultraviolet Raman spectrometer system. The portable Raman improvised explosives detector was designed to provide rapid, standoff detection of chemicals of interest to the end user, including, but not limited to explosives, narcotics, toxic industrial chemicals, and toxic industrial materials. In this paper, we discuss general aspects of the system design and user interface. Spectral and instrument performance data are shown for several common materials involved in narcotics manufacture, as well as cocaine and heroin, with comparisons to currently marketed handheld Raman instruments.
Neurological manifestations of scrub typhus in adults
Authors: Rana Abhinav , Mahajan Sanjay K , Sharma Arindam , Sharma Sudhir , Verma Balbir S , Sharma Ashok
Published: April 2016

In order to study the neurological manifestations in adult patients suffering from scrub typhus, 323 patients aged over 18 years, admitted with a positive diagnosis, were screened for neurological dysfunction; 37 patients with symptoms and/or signs suggestive of neurological dysfunction were included in the study. Of these, 31 (84%) patients had altered sensorium, four (11%) had cerebellitis, one (2%) patient had acute transverse myelitis and one (2%) had bilateral papilloedema without focal neurological deficit. Of the 31 patients with altered sensorium, 15 (40%) had meningoencephalitis, three (8%) had seizures, two (5%) had cerebral haemorrhages, one (2%) had a presentation likened to neuroleptic malignant syndrome (NMS) and one (2%) had a 6th nerve palsy with inflammation of the right cavernous sinus. Cerebrospinal fluid (CSF) analysis was abnormal in 23 patients (raised lymphocytes in 68%, raised protein in 80%). All patients improved with anti-rickettsial therapy.
Tonsillectomy and Adenoidectomy: Incidence and Mortality, 1968–1972
Authors: Pratt Loring W. , Gallagher Ruth A.
Published: April 2016

To determine the number of tonsillectomies and adenoidectomies (T‐As) from 1968 to 1972 and their associated morbidity and mortality rates, a questionnaire was sent to all the hospitals listed in the Directory of the American Hospital Association (6,759). The data were analyzed and statistical projections were made. An analysis was also made of the summary report of the “Study on Surgical Services for the United States,” with regard to the incidence of T‐A was also made. The results are presented in the following report.
Mucoceles of The Sphenoid Sinus
Authors: Weaver Robert G. , Gates George A.
Published: April 2016

Mucoceles of the sphenoid sinuses are uncommon; 60 cases have been reported in the world literature to date. Signs and symptoms are caused by local expansion of the mucocele and include headache (the most common symptom), ocular field deficits, external ophthalmoplegia (particularly the sixth cranial nerve), and proptosis. Radiologic correlation in the form of plain films and polytomography is the most reliable guide in the diagnosis of sphenoid sinus disease. Therapy of these lesions is surgical, and drainage can be achieved via the external ethmoid or sublabial transseptal route.

Three cases are presented: two had classical findings and the third was conspicuous by the presence of aseptic meningitis in the absence of local findings.
Dacryocystorhinostomy Utilizing an Anterior Lacrimal Sac Flap to Periosteum Technique
Authors: Holt G. Richard , Holt Jean Edwards , Cortez Edwin A.
Published: April 2016

Dacryocystorhinostomy is used in the effective treatment of epiphora secondary to obstruction of the lacrimal drainage system. Common causes of obstruction include canalicular disruption, lacrimal sac fibrosis, and external and internal nasal trauma.

Most techniques of dacryocystorhinostomy attempt to suture the lacrimal sac mucosa to the nasal mucosa. At best this is technically difficult, and the mucosa frequently tears. A technique is presented using an anteriorly based lacrimal sac pedicle flap sutured to the periosteum of the anterior lacrimal crest. The sutured flap is quite strong, and the procedure is technically simpler than others.

A brief description of the causes of lacrimal obstruction is given. The Jones primary and secondary dye tests for lacrimal system patency are reviewed.
Osteomyelitis of The Mandibular Condyle Secondary to Dental Extractions
Authors: Wurman Leonard H. , Flannery John V. , Sack J. Garry
Published: April 2016

Although osteomyelitis of the mandibular condyle secondary to dental extraction is scarcely mentioned in the medical and dental literature, we have seen three cases within a two‐year period. The first two patients were examined for an eroded condyle three months and 18 months following the extractions. The third patient, who was treated one month after extraction for acute osteomyelitis of the condyle, has done well. All three patients required operations and administration of long‐term antibiotics.
Anatomy of The Subglottic Larynx
Authors: Carter Donald R. , Meyers Arlen D.
Published: April 2016

There is little concensus concerning the boundaries of the subglottic space. To better define the subglottis, 50 head and neck surgeons were asked to define its anatomic limits. In addition, the larynx of each of 25 male and 25 female adult cadavers was removed, and four measurements in the anterior subglottis were taken. The results revealed significantly smaller subglottic dimensions for the women than for the men.
Intranasal Corticosteroid Injection: Indications, Technique, and Complications
Authors: Mabry Richard L.
Published: April 2016

The intranasal injection of corticosteroids for symptomatic relief of nasal obstruction in selected cases has been described by several authors1–8and widely used for over 25 years. Recently, circulated reports of blindness following such injections caused a number of otolaryngologists to discontinue using the procedure. All reported cases of visual complications following intranasal corticosteroid injection are reviewed,9,12,13,17together with the reported experiences of the author20and others15–17who have successfully used the technique in thousands of cases. Preliminary topical cocainization of nasal mucosa and slow submucosal injection of a micronized corticosteroid suspension to minimize the risk of vasospasm and embolization involving the ophthalmic circulation are stressed. Indications for the procedure, the most common side effects, and the proper technique of injection are described.