bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Richter Syndrome Xenograft Models to Study Genetic Architecture, Biology, and Therapy Responses
Authors: Vaisitti Tiziana , Braggio Esteban , Allan John N. , Arruga Francesca , Serra Sara , Zamò Alberto , Tam Wayne , Chadburn Amy , Furman Richard R. , Deaglio Silvia
Published: May 2018

Richter syndrome represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B-cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemoimmunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft (PDX) models of Richter syndrome, RS9737 and RS1316. Richter syndrome xenografts were genetically, morphologically, and phenotypically stable and similar to the corresponding primary tumor. RS9737 was characterized by biallelic inactivation of CDKN2A and TP53, monoallelic deletion of 11q23 (ATM), and mutations of BTK, KRAS, EGR2, and NOTCH1. RS1316 carried trisomy 12 and showed mutations in BTK, KRAS, MED12, and NOTCH2. RNA sequencing confirmed that in both cases >80% of the transcriptome was shared between primary tumor and PDX. In line with the mutational profile, pathway analyses revealed overactivation of the B-cell receptor, NFκB, and NOTCH pathways in both tumors, potentially providing novel tumor targets. In conclusion, these two novel models of Richter syndrome represent useful tools to study biology and response to therapies of this highly aggressive and still incurable tumor.

Significance: Two patient-derived xenograft models of Richter syndrome represent the first ex vivo model to study biology of the disease and to test novel therapeutic strategies. Cancer Res; 78(13); 3413–20. ©2018 AACR.
Optimized Dosing Schedule Based on Circadian Dynamics of Mouse Breast Cancer Stem Cells Improves the Antitumor Effects of Aldehyde Dehydrogenase Inhibitor
Authors: Matsunaga Naoya , Ogino Takashi , Hara Yukinori , Tanaka Takahiro , Koyanagi Satoru , Ohdo Shigehiro
Published: May 2018

Although malignant phenotypes of triple-negative breast cancer (TNBC) are subject to circadian alterations, the role of cancer stem cells (CSC) in defining this circadian change remains unclear. CSC are often characterized by high aldehyde dehydrogenase (ALDH) activity, which is associated with the malignancy of cancer cells and is used for identification and isolation of CSC. Here, we show that the population of ALDH-positive cells in a mouse 4T1 breast tumor model exhibits pronounced circadian alterations. Alterations in the number of ALDH-positive cells were generated by time-dependent increases and decreases in the expression of Aldh3a1. Importantly, circadian clock genes were rhythmically expressed in ALDH-negative cells, but not in ALDH-positive cells. Circadian expression of Aldh3a1 in ALDH-positive cells was dependent on the time-dependent release of Wingless-type mmtv integration site family 10a (WNT10a) from ALDH-negative cells. Furthermore, antitumor and antimetastatic effects of ALDH inhibitor N,N-diethylaminobenzaldehyde were enhanced by administration at the time of day when ALDH activity was increased in 4T1 tumor cells. Our findings reveal a new role for the circadian clock within the tumor microenvironment in regulating the circadian dynamics of CSC. These results should enable the development of novel therapeutic strategies for treatment of TNBC with ALDH inhibitors.

Significance: This seminal report reveals that circadian dynamics of CSC are regulated by the tumor microenvironment and provides a proof of principle of its implication for chronotherapy in TNBC. Cancer Res; 78(13); 3698–708. ©2018 AACR.
Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures Into Future Successes
Authors: Winer Arthur , Adams Sylvia , Mignatti Paolo
Published: May 2018

The matrix metalloproteinases (MMP) are a family of proteolytic enzymes that degrade multiple components of the extracellular matrix. A large body of experimental and clinical evidence has implicated MMPs in tumor invasion, neoangiogenesis, and metastasis, and therefore they represent ideal pharmacologic targets for cancer therapy. From the 1990s to early 2000s, synthetic inhibitors of MMPs (MMPI) were studied in various cancer types. Unexpectedly, despite strongly promising preclinical data, all trials were unsuccessful in reducing tumor burden or improving overall survival; in addition, MMPIs had unforeseen, severe side effects. Two main reasons can explain the failure of MMPIs in clinical trials. It has now become apparent that some MMPs have antitumor effects; therefore, the broad-spectrum MMPIs used in the initial trials might block these MMPs and result in tumor progression. In addition, although MMPs are involved in the early stages of tumor progression, MMPIs were tested in patients with advanced disease, beyond the stage when these compounds could be effective. As more specific MMPIs are now available, MMP targeting could be reconsidered for cancer therapy; however, new trials should be designed to test their antimetastatic properties in early-stage tumors, and endpoints should focus on parameters other than decreasing metastatic tumor burden. Mol Cancer Ther; 17(6); 1147–55. ©2018 AACR.
Real-Time-Monitoring in der Behandlung komplexer posttraumatischer Belastungsstörung: Ein Fallbericht
Authors: Kratzer Leonhard , Heinz Peter , Pfitzer Franz , Schennach Rebecca , Aichhorn Wolfgang , Aas Benjamin , Schiepek Günter
Published: May 2018

Hintergrund: Anhand eines Fallbeispiels soll gezeigt werden, wie Real-Time-Monitoring die Therapie von PatientInnen mit komplexer posttraumatischer Belastungsstörung (PTBS) wirksamer gestalten hilft. Patient und Methoden: Die Fallkonzeption und Behandlung fußten auf einem störungsspezifischen stationären Behandlungsprogramm für komplex traumatisierte Erwachsene und orientierten sich an Empfehlungen bezüglich der traumafokussierten Behandlung von Patienten mit pathologischem Narzissmus. Der Veränderungsprozess des Patienten wurde mit einem webgestützten Tool für Real-Time-Monitoring (Synergetic Navigation System) erfasst und im Therapieverlauf wiederholt gemeinsam mit dem Patienten reflektiert. Ergebnisse: Der Patient remittierte hinsichtlich PTBS, Depression, somatoformer Beschwerden, interaktioneller Schwierigkeiten, Selbstwirksamkeit und Beeinträchtigungen des psychischen Wohlbefindens. Insbesondere konnten im Rahmen von Feedback-Gesprächen die persönlichkeitsspezifischen affektiven Dynamiken von Scham, Schuld und Wut des Patienten sowie deren kritische Instabilitäten und Phasenübergänge im Rahmen der Traumakonfrontation reflektiert werden. Der Patient entwickelte neue Selbstfürsorgemuster und lernte, eigene Gefühle wahrzunehmen, zu verantworten und zu regulieren. Schlussfolgerungen: Die auf Traumakonfrontation ausgerichtete multimodale Therapie erwies sich im vorliegenden Fall als geeignet, neben den Kernsymptomen der PTBS auch bedeutsame komorbide Symptome wirksam zu reduzieren. Das Real-Time-Monitoring unterstützt die Identifizierung und Bearbeitung zentraler affektiver Dynamiken eines Patienten und erlaubt so, die Therapie von Patienten mit komplexen Traumafolgestörungen und persönlichkeitsprägender Symptomatik effektiver zu gestalten.
A Systematic Review and Meta-Analysis of the Effectiveness of Acetylcholinesterase Inhibitors and Memantine in Treating the Cognitive Symptoms of Dementia
Authors: Knight Ruth , Khondoker Mizanur , Magill Nicholas , Stewart Robert , Landau Sabine
Published: May 2018

Background: Acetylcholinesterase inhibitors (AChEIs) and memantine are commonly used in the management of dementia. In routine clinical practice, dementia is often monitored via the Mini-Mental State Examination (MMSE). We conducted a systematic review and meta-analysis of the effects of these drugs on MMSE scores. Summary: Eighty trials were identified. Pooled effect estimates were in favour of both AChEIs and memantine at 6 months. Meta-regression indicated that dementia subtype was a moderator of AChEI treatment effect, with the effect of treatment versus control twice as high for patients with Parkinson disease dementia/ dementia with Lewy bodies (2.11 MMSE points at 6 months) as for patients with Alzheimer disease/vascular dementia (0.91 MMSE points at 6 months). Key Messages: AChEIs demonstrate a modest effect versus control on MMSE scores which is moderated by dementia subtype. For memantine the effect is smaller.
Anti-PD-1 Therapy Leads to Near-Complete Remission in a Patient with Metastatic Basal Cell Carcinoma
Authors: Fischer Stefanie , Ali Omar H. , Jochum Wolfram , Kluckert Thomas , Flatz Lukas , Siano Marco
Published: May 2018

Background: Metastatic basal cell carcinoma is rare and the prognosis is poor, with a lack of established treatment options for patients progressing on or after treatment with inhibitors of the hedgehog signaling pathway. Case Report: A man with pulmonary metastases of a basal cell carcinoma progressing after treatment with sonidegib and vismodegib was started on treatment with the anti-PD-1 antibody pembrolizumab. Upon treatment, rapid clinical improvement occurred, and after 5 cycles, the computed tomography scan showed near-complete remission of all tumor lesions. The tumor cells showed the absence of PD-L1 expression. Discussion: We report the first case of a patient with metastatic basal cell carcinoma experiencing an exceptional response to treatment with pembrolizumab in the absence of PD-L1 expression on the tumor cells. Immune checkpoint inhibition seems a promising treatment strategy for metastatic basal cell carcinoma. Our case suggests that the lack of PD-L1 expression does not rule out potential benefit from checkpoint inhibitor treatment.
Mortalitätsrisiko von älteren Menschen mit Bronchialobstruktion - die prognostische Relevanz von Grenzwerten
Authors: Frohnhofen Helmut
Published: May 2018

Background: Whether a fixed cutoff or the lower limit of normal of the FEV1/FVC ratio should be used to diagnose bronchial obstruction is still a matter of debate. This issue is particularly important for elderly people. Objectives: We used equations applicable up to 90 years of age to evaluate the mortality of elderly people diagnosed with bronchial obstruction using either a fixed cutoff of 0.7 or the lower limit of normal (LLN). Methods: Participants in the SaRA (Salute Respiratoria nell'Anziano, Italian for “Respiratory Health in the Elderly”) study were grouped as follows: FEV1/FVC ≥0.7 and ≥ LLN (n = 535: F-/L--), FEV1/FVC <0.7 but ≥ LLN (n = 118: F+/L-), and FEV1/FVC <0.7 and < LLN (n = 229: F+/L+). We estimated the mortality risk in the three groups over 15 years of follow-up. Results: The mean age was 73 years (58% men). The hazard ratio (HR) for mortality was 1.427 (95% CI: 1.09-1.868) in the F+/L- group and 2.143 (95% CI: 1.13-1.995) in the F+/L+ group. After adjustment for potential confounders, we found no increased mortality in the F+/L- group (HR: 1.007, 95% CI: 0.755-1.342), while the HR in the F+/L+ group was still sizeable (1.474, 95% CI: 1.136-1.911). Conclusions: As expected, using a fixed cutoff translates in a larger number of people to be classified as having bronchial obstruction. In our sample the increased mortality in the F+/L- group is due to the confounding effect of age and sex. Our study lends support to the use of LLN in elderly people.
Transbronchiale Kryobiopsien in der Diagnostik diffuser interstitieller Lungenerkrankungen: Sicherheit, Einsetzbarkeit und Standardisierung des Verfahrens
Authors: Stanzel Franz
Published: May 2018

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27-28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diag- nostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.
Hybrid Revascularization: A Review
Authors: Saha Tisa , Naqvi Syed Yaseen , Goldberg Sheldon
Published: May 2018

Hybrid coronary revascularization (HCR) combines surgical bypass with percutaneous coronary intervention (PCI) performed either during the same procedure or in a staged approach within 60 days. Coronary artery bypass grafting using the left internal mammary artery (LIMA) has shown excellent long-term patency with improved patient survival. It remains the gold standard treatment for the majority of patients with multivessel coronary artery disease. However, saphenous vein grafts have poor long-term patency. Advances in stent technology have resulted in reduced rates of thrombosis and restenosis, making PCI a viable alternative to coronary surgery in selected patients. HCR is attractive as a less invasive method of coronary revascularization which preserves the benefits of the LIMA performed with less invasive surgical techniques with the efficacy of newer generation stents.
Which Fruits and Vegetables Should Be Excluded from a Low-Salicylate Diet? An Analysis of Salicylic Acid in Foodstuffs in Taiwan
Authors: Chiang Hui-Ling , Venter Carina , Syue Pai-Chi , Ku Kuo-Lung , Wu Cheng-Han
Published: May 2018

Background: Eliminating pseudoallergens is an important element of managing chronic spontaneous urticaria (CSU). Salicylic acid (SA) is a primary pseudoallergen in plant-based foodstuffs. Current dietary recommendations are not applicable in East Asia because data on the SA content of many vegetables and fruits commonly consumed in this region are lacking. Methods: We therefore determined the concentration of free SA in 79 popular vegetables and fruits frequently consumed in Taiwan using gas chromatography-mass spectrometry. Results: The SA content ranged from 0.09 to 2.3 mg/kg in the fresh vegetables examined, and from 0.01 to 0.48 mg/kg in the fruits. Conclusions: Data regarding the SA content of East Asian vegetables and fruits could help CSU patients limit their pseudoallergen consumption.
Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory
Authors: Tsai Sheng-Feng , Ku Nai-Wen , Wang Tzu-Feng , Yang Yan-Hsiang , Shih Yao-Hsiang , Wu Shih-Ying , Lee Chu-Wan , Yu Megan , Yang Ting-Ting , Kuo Yu-Min
Published: May 2018

Background: Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Objective: Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Methods: Young (3 months), middle-aged (9–12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. Results: The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. Conclusion: The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline.
The Self in the Spectrum: A Closer Look at the Temporal Stability of Self-Disorders in Schizophrenia
Authors: Raballo Andrea , Preti Antonio
Published: May 2018

Self-disorders are temporally persisting, experiential anomalies of subjective experiences that index liability to schizophrenia. They impact on the temporal unfolding of concomitant, diagnostic symptoms and can be suitably characterized through the Examination of Anomalous Self Ex periences (EASE). Capitalizing on the results of a recent longitudinal study, we explored the relevant patterns of interaction within self-disorders’ descriptive dimensions (i.e., stream of consciousness, presence, corporeality, demarcation, and solipsism). The results indicated that after a 5-year follow-up the interconnection across SD dimensions tightened, confirming that EASE domains are interdependent aspects of an overarching structural change of subjectivity.
MicroRNA-135a Inhibits Nasopharyngeal Carcinoma Cell Proliferation Through Targeting Interleukin-17
Authors: Wang Li-Xin , Kang Zhao-Peng , Yang Zhi-Chao , Ma Rui-Xia , Tan Yan , Peng Xian-Bing , Dai Run-Zhi , Li Jin , Yu Yang , Xu Min
Published: May 2018

Background/Aims: The objective of this study was to investigate the potential role of IL-17 in the development of nasopharyngeal carcinoma (NPC) and to screen microRNAs (miRNAs) that potentially target IL-17 in NPC cells. Methods: Blood was collected from NPC patients and normal subjects, and plasma IL-17 concentration was quantified by enzyme-linked immunosorbent assay. An immortalized normal human nasopharyngeal epithelial cell line, NP69, was treated with or without human IL-17 (15 ng/mL) for various times, and expression of IL-1ß, IL-6, IL-12, and TNF-α mRNA was assessed by real-time reverse transcription PCR. The candidate miRNAs that potentially target IL-17 were predicted by a bioinformatics strategy. The selected miR-135a mimic was transfected into primary NPC cells, and cell proliferation was assessed by MTT assay. Results: The concentration of plasma IL-17 was significantly higher in the NPC patients (92.5 ± 7.3 pg/mL) than in the control subjects (56.8 ± 2.9 pg/mL). In response to IL-17 treatment, the mRNA expression of IL-1ß and IL-6 was significantly upregulated and reached a peak at 12 h, followed by a slight decrease at 24 h, while the mRNA expression of IL-12 and TNF-α was significantly upregulated at 12 h and remained high even at 48 h after exposure to IL-17. Moreover, miR-135a specifically targets IL-17 and was dramatically downregulated in NPC cells compared with NP69 cells. Transfection of exogenous miR-135a mimic resulted in significant suppression of IL-17 secretion and subsequent inhibition of NPC cell proliferation. Conclusions: Blood IL-17 was significantly higher in NPC patients compared with normal subjects. Expression of miR-135a in the cancer cells isolated from nasopharyngeal tumors was significantly lower than that in NP69 cells, and suppression of IL-17 by miR-135a mimic resulted in significant inhibition of NPC cell proliferation. These findings suggested that downregulation of miR-135a may contribute to the development of NPC via the mechanism of IL-17 stimulation of proinflammatory cytokine expression.
Expression Profiling of Circular RNAs and Micrornas in Heart Tissue of Mice with Alcoholic Cardiomyopathy
Authors: Yang Yuqiao , Chen Hongmei , Ding Nina , Wang Shuo , Duan Zhantao , Birnbaum Yochai , Ye Yumei , Qian Jinqiao
Published: May 2018

Background/Aims: Chronic heavy alcohol consumption may result in alcoholic cardiomyopathy. This study was designed to screen differentially expressed microRNAs and circular RNAs in heart tissue of mice with alcoholic cardiomyopathy to reveal the underlying molecular mechanism. Methods: Having established a murine alcoholic cardiomyopathy model, we screened differentially expressed microRNAs and circular RNAs in three heart samples from the alcohol-treated and control groups by high-throughput microarray analysis. We analyzed the function and biological signaling pathways of differentially expressed non-coding RNAs closely related to alcoholic cardiomyopathy using bioinformatics software to identify some mRNAs and their biological signaling pathways closely related to alcoholic cardiomyopathy. Results: Nineteen microRNAs and 265 circular RNAs were differentially expressed in the alcohol-treated group compared with the control group. After analyzing gene function and signaling pathways by bioinformatics software, we found that the differentially expressed mRNAs were associated with carbohydrate metabolism. Conclusions: Chronic alcohol consumption can change the non-coding RNA profile of heart tissue, which is closely related to the pathological mechanisms of alcoholic cardiomyopathy.
Mitofusin 2 Exerts a Protective Role in Ischemia Reperfusion Injury Through Increasing Autophagy
Authors: Peng Cheng , Rao Wei , Zhang Lei , Gao Fan , Hui Hao , Wang Kai , Dai Shuhui , Yang Yuefan , Luo Peng , Ma Yihui , Ma Wenke , Yu Xinguang , Fei Zhou
Published: May 2018

Background/Aims: Autophagy is essential for maintaining cellular homeostasis and the survival of terminally differentiated cells as neurons. In this study, we aim to investigate whether mitofusin 2, a mitochondrial fusion protein, mediates autophagy in cerebral ischemia/reperfusion (I/R) injury. Methods: Primary cultured neurons were treated with oxygen-glucose deprivation/reperfusion to mimic cerebral I/R injury in vitro. Autophagosomes were visualized upon TEM. Autophagy-markers were then detected to monitor autophagy by western-blot and real-time PCR, and the autophagic flux was tracked with a mRFP-GFP-LC3 construct by fluorescence as well as autophagy inhibitors and agonists. The up- and downregulation of Mfn2 were through transfecting a lentivirusexpression vector respectively. And neuronal injury was detected by cell counting kit and TUNEL assay. Results: Results showed I/R increased autophagosome formation and inhibited autolysosome degradation. Furthermore, use of autophagy related agents demonstrated that I/R injury was caused by insufficient autophagy and aggravated by impaired autophagic degradation. The results also indicated that mitofusin 2 could ameliorate I/R injury through increasing autophagosome formation and promoting the fusion of autophagosomes and lysosomes. In contrast, downregulation of mitofusin 2 aggravated the I/R injury by inhibiting autophagosome formation and the fusion of autophagosomes and lysosomes. Additionly, mitofusin 2 overexpression did not lead to autolysosome accumulation induced by I/R. Conclusions: In summary, this study explicitly demonstrated that mitofusin 2 could ameliorate I/R injury mainly through promoting autophagy, which represented a potential novel strategy for neuroprotection against cerebral I/R damage.
Cell-Based Therapies in Acute Kidney Injury (AKI)
Authors: Patschan Daniel , Buschmann Ivo , Ritter Oliver , Kribben Andreas
Published: May 2018

Acute kidney injury frequently occurs in hospitalized patients all over the world. The prognosis remains poor since specific therapies for promoting kidney regeneration/repair are still missing. In recent years cell-based strategies have improved AKI outcomes under experimental circumstances. Four groups of cells, each of them displaying certain biological and functional characteristics have been evaluated in AKI, induced Pluripotent Stem Cells (iPSCs), Spermatagonial Stem Cells (SSCs), Proangiogenic Cells (PACs) and Endothelial Colony Forming Cells (ECFCs), and Mesenchymal Stem Cells (MSCs). All of these have been documented to stabilize either parameters of kidney excretory dysfunction and/or certain morphological parameters. The mechanisms responsible for AKI protection include direct (cell incorporation) and indirect processes, the latter being mediated by humoral factors and particularly by the production of so-called extracellular vesicles. Cell-derived vesicular organelles have been shown to carry pro-regenerative micro-RNA molecules which stabilize the vascular and tubular function. The first trials in humans have been initiated, the majority of such trials employs MSCs. However, any transfer of cell-based strategies in the clinical practice is potentially associated with significant difficulties. These include cell availability, tolerance and competence. The article intends to summarize essential informations about all of the four populations mentioned above and to discuss implications for the management of human AKI.
As Cetariae na Província da Hispânia Bética: O Garum enquanto Continuação de uma Prática Econômica e Cultural Fenício-Púnico em Gades e sua Ressignificação em Contexto Romano
Authors: Lima Rodrigo Araújo de
Published: May 2018

Produzidos nas cetariae da Hispânia Bética o garum e seus derivados foram iguarias alimentares introduzida na dieta latina tanto por suas qualidades gastronômicas e medicinais quanto pelo seu status. Neste artigo descreveremos a continuação da prática das salgações fenícias e púnicas estabelecidas na cidade fenícia de Gádir, mantida na Gades romana e absorvida pela dieta romana.
Evaluation of Sildenafil and Tadalafil for Reversing Constriction of Fetal Arteries in a Human Placenta Perfusion Model
Authors: Walton Robert B. , Reed Luckey C. , Estrada Sarah M. , Schmiedecke Stacey S. , Villazana-Kretzer Diana L. , Napolitano Peter G. , Ieronimakis Nicholas
Published: May 2018

Fetal growth restriction resulting from reduced placental blood perfusion is a major cause of neonatal morbidity and mortality. Aside from intense surveillance and early delivery, there is no treatment for fetal growth restriction. A potential treatment associated with placental vasoconstriction is the class of PDE5 (phosphodiesterase type 5) inhibitors such as sildenafil, which is known to cross the placenta. In contrast, tadalafil, a more potent and selective PDE5 inhibitor has not been studied in pregnancy or experimental models of fetal growth restriction. Therefore, we compared the efficacy of these 2 PDE5 inhibitors for reversing vasoconstriction in an ex vivo human placental model and evaluating molecular and physiological responses. Sildenafil and tadalafil were infused into the intervillous space in a preconstricted human placental dual cotyledon, dual perfusion assay for the comparison of arteriole pressures and molecular indicators of drug inhibition. Results indicate a decrease arterial pressure with sildenafil citrate compared with controls, whereas tadalafil showed no difference. PDE5 and endothelial nitric oxide synthase activity were altered with sildenafil but not tadalafil. Sildenafil citrate improved preconstricted placental arterial perfusion in a human placental model, whereas tadalafil showed no response. It is possible that tadalafil did not cross the human placental barrier or was degraded by trophoblasts. This study supports human clinical trials exploring sildenafil as a potential treatment for improving fetal blood flow in fetal growth restriction associated with vasoconstriction.
The Promise of the Road: Legal Peasant Movement for Short Distances and the Limits of Serfdom
Authors: Bohac Rodney
Published: May 2018

Russian serfdom was characterized by the tension between the need of the state and of the nobility to restrict peasant mobility and the simultaneous need of both parties to keep peasants moving in order for the economy to function. Previous studies have examined this movement through the lens of long-distance peasant migration. This article shifts the focus to short-distance movement in which serfs traveled on their estates, to neighboring villages, and to nearby towns and cities. Serfs journeyed in order to carry freight for themselves and for their serfowners, to conduct business at nearby markets and district towns, and to find work. Travel brought many dangers for peasants, which could result in economic and physical harm. Peasants endured these hardships because the road offered the advantages of financial gain and the pleasures of social interaction. Moreover, travel offered moments of autonomy during which serfs were not directly supervised by their owners. Some serfs enjoyed their autonomy so much that they changed the itineraries on their travel documents, moved beyond the spatial or temporal limits of their documents, or engaged in flight in an effort to escape the personal control of their owner.
Revision of the Oriental genus Zavatilla Tsuneki (Hymenoptera, Mutillidae, Trogaspidiini), with descriptions of two new species
Authors: ZHOU HU-TING , LELEJ ARKADY S. , WILLIAMS KEVIN A. , LIU JING-XIAN
Published: May 2018

Four species of the genus Zavatilla Tsuneki, 1993 are reviewed. An updated diagnosis of the genus is given and two new sex associations are proposed. Two new species, Z. xuzaifui Zhou, Lelej et Williams, sp. nov. (China: Guangdong, Yunnan, Hainan; Vietnam) and Z. nepalensis Zhou et Lelej, sp. nov. (Nepal) are described. Mutilla logei Zavattari, 1913 is proposed as junior synonym of Z. gutrunae (Zavattari, 1913). The status of Z. gutrunae flavotegulata (Chen, 1957) is updated to specific level. A key to the known species of Zavatilla is given for males and females.
The Relationship between Cool and Warm Season Moisture over the Central United States, 1685–2015
Authors: Torbenson Max C. A. , Stahle David W.
Published: May 2018

Land surface feedbacks impart a significant degree of persistence between cool and warm season moisture availability in the central United States. However, the degree of correlation between these two variables is subject to major changes that appear to occur on decadal to multidecadal time scales, even in the relatively short 115-yr instrumental record. Tree-ring reconstructions have extended the limited observational record of long-term soil moisture levels, but such reconstructions do not resolve the seasonal differences in moisture conditions. We present two separate 331-yr-long seasonal moisture reconstructions for the central United States, based on sensitive subannual and annual tree-ring chronologies that have strong and separate seasonal moisture signals: an estimate of the long-term May soil moisture balance and a second estimate of the short-term June–August atmospheric moisture balance. The predictors used in each seasonal reconstruction are not significantly correlated with the alternate season target. Both reconstructions capture over 70% of the interannual variance in the instrumental data for the calibration period and also share significant decadal and multidecadal variability with the instrumental record in both the calibration and validation periods. The instrumental and reconstructed moisture levels are both positively correlated between spring and summer strongly enough to have potential value in seasonal prediction. However, the relationship between spring and summer moisture exhibits major decadal changes in strength and even sign that appear to be related to large-scale ocean–atmosphere dynamics associated with the Atlantic multidecadal oscillation.
Evaluating the Experimental High-Resolution Rapid Refresh–Alaska Modeling System Using USArray Pressure Observations
Authors: McCorkle Taylor A. , Horel John D. , Jacques Alexander A. , Alcott Trevor
Published: May 2018

The High-Resolution Rapid Refresh–Alaska (HRRR-AK) modeling system provides 3-km horizontal resolution and 0–36-h forecast guidance for weather conditions over Alaska. This study evaluated the experimental version of the HRRR-AK system available from December 2016 to June 2017, prior to its operational deployment by the National Centers for Environmental Prediction in July 2018. Surface pressure observations from 158 National Weather Service (NWS) stations assimilated during the model’s production cycle and pressure observations from 101 USArray Transportable Array (TA) stations that were not assimilated were used to evaluate 265 complete 0–36-h forecasts of the altimeter setting (surface pressure reduced to sea level). The TA network is the largest recent expansion of Alaskan weather observations and provides an independent evaluation of the model’s performance during this period. Throughout the study period, systematic differences in altimeter setting between the HRRR-AK 0-h forecasts were larger relative to the unassimilated TA observations than relative to the assimilated NWS observations. Upon removal of these initial biases from each of the subsequent 1–36-h altimeter setting forecasts, the model’s 36-h forecast root-mean-square errors at the NWS and TA locations were comparable. The model’s treatment of rapid warming and downslope winds that developed in the lee of the Alaska Range during 12–15 February is examined. The HRRR-AK 0-h forecasts were used to diagnose the synoptic and mesoscale conditions during this period. The model forecasts underestimated the abrupt increases in the temperature and intensity of the downslope winds with smaller errors as the downslope wind events evolved.
Whiteness as a Dissonant State: Exploring One White Male Student Teacher’s Experiences in Urban Contexts
Authors: Behm Cross Stephanie , Tosmur-Bayazit Nermin , Dunn Alyssa Hadley
Published: May 2018

Studies on student teaching continue to suggest that preservice teachers’ feelings of dissonance are related to disparate views of teaching and learning between universities and schools. Drawing on interview, artifact, and observation data, the authors utilize Cognitive Dissonance and Critical Whiteness Studies to make different sense of the experiences of one White student teacher (Brett). Results indicate that Brett experienced dissonance related to fractured relationships, misaligned teaching strategies, and disengagement as he taught youth of color. Importantly, the use of Critical Whiteness Studies helped to additionally reveal the way Whiteness affected Brett’s movements toward consonance—mainly through rationalization and problematic notions of perseverance. The authors suggest that Whiteness itself is a dissonant state, and argue that conversations focused on dissonance from misaligned university theory and K-12 schooling practices is dangerously incomplete. Implications for research and practice are included.
Why Men and Women Want to Leave? Turnover Intent Among Public Procurement Officers
Authors: Ali Susannah Bruns , Bishu Sebawit , Alkadry Mohamad
Published: May 2018

This study examines differences in turnover intent between men and women with the aim of building a better understanding of factors that contribute to disparities between the sexes and creating more useful recruitment and retention strategies. The study proposes a theoretical framework where personal, human capital, organizational, and structural/community factors contribute to the desire to change jobs. The focus here is on procurement officers as their role is critical in public sector organizations from the local to the federal level. They also are unique in that their skill set is transferable from one organization to another and procurement officers have relatively high opportunities to move both within and between organizations. The study finds that there are important differences in the drivers of turnover intent between men and women and that most differences lie in the personal, human capital, and organizational categories.
The politics of creditor–debtor relations and mortgage payment strikes: The case of the Uruguayan Federation of Mutual-Aid Housing Cooperatives
Authors: Vidal Lorenzo
Published: May 2018

Mortgage debt and concomitant forms of financial expropriation continue their largely uncontested expansion across the social terrain. The atomisation of debtors and commodity fetishism are two key factors that underpin this process. The collective and partially de-commodified character of mutual-aid housing cooperatives in Uruguay and their conflict-ridden mortgage debt relations provide a contrasting, reverse mirror image. This paper analyses how in the case of a collective debtor, the spatial fixity and temporal uncertainties that result from the establishment of mortgage debt relations can work against the creditor. Housing cooperatives make up a geography of spaces that are opaque to the creditor, in the sense that mortgage debtors cannot be individually identified and pursued. Once homes are constructed and inhabited, the creditor’s debt claims can be collectively challenged. In the context of the most recent mortgage payment strike (2001–2011) carried out by the Uruguayan Federation of Mutual-Aid Housing Cooperatives, what is presumed a voluntary contract between equal parties is revealed as a power struggle between owners and non-owners of capital. This atypical case provides an opportunity to empirically attest to the political nature of creditor–debtor relations, often rendered socially invisible due to the extreme power imbalance between counterparties.
Cephalic cutaneous allodynia in children and adolescents with migraine of short duration: A retrospective cohort study
Authors: Levinsky Yoel , Zeharia Avraham , Eidlitz-Markus Tal
Published: May 2018

Background

Allodynia is prevalent in adults with migraine and has been associated with long disease duration and severe course. Studies of the pediatric population are sparse. The aim of this study was to evaluate the rate of cephalic cutaneous allodynia in children and adolescents within the first 6 months of migraine onset and to identify associated clinical and migraine-related parameters.

Methods

The electronic database of a tertiary pediatric headache clinic from 2014 to 2017 was retrospectively searched for all children and adolescents diagnosed with migraine headache within 6 months or less of symptom onset. Cephalic cutaneous allodynia was identified by validated questionnaire. Demographics, symptoms, and headache-related parameters were compared between patients with and without allodynia.

Results

The cohort included 119 patients, 69 girls (58.0%) and 50 (42.0%) boys, of mean age 11.6 ± 3.6 years. Mean time since onset of migraine disease was 3.6 ± 1.8 months. Cephalic cutaneous allodynia was reported by 31.1% of patients. It was significantly associated with female gender ( p = 0.03), older age at admission ( p = 0.037), older age at onset ( p = 0.042) migraine with aura ( p = 0.002), and higher rate of awakening pain ( p = 0.017).

Conclusions

Cephalic cutaneous allodynia may occur in children and adolescents already in the first 6 months of migraine onset. Contrary to adult studies, we found no association of allodynia with migraine frequency or long disease duration. Allodynia was significantly associated with migraine with aura, female gender, and awakening pain. A genetic tendency may contribute to the appearance of allodynia in the pediatric age group.
Can Capitalism Be Truly Democratic?
Authors: Artner Annamária
Published: May 2018

This article re-examines the relationship between the liberal democracy and the free market with special regard to changes caused by globalization. It concludes that the logic of market mechanisms poses a threat to democracy, while the extension of democracy would inevitably limit the freedom of the market and curb capital accumulation. The globalized free market and liberal democracy contradict each other, and their tandem may be the most developed form of capitalism, but not of human society in general.
Examining Comprehension Strategy Instruction With English Learners’ Problem Solving: Study Findings and Educator Preparation Implications
Authors: Orosco Michael J. , Abdulrahim Naheed A.
Published: May 2018

Educator preparation in comprehension strategy instruction (CSI) is essential to meeting the needs of English learners (ELs) in contemporary schools. This article provides teacher educators and professional developers with concrete examples of practices to prepare classroom teachers in comprehensive strategy instruction, based on an experimental study that examined the effect (.37) of CSI on third-grade students’ ( n = 78) word-problem-solving (WPS) performance. CSI included problem-solving strategies that (a) helped students to understand the relevant and irrelevant information in a word problem’s question; (b) helped students to restate the problem orally, which allowed them to understand, to construct meaning, and to clarify any misunderstanding about the question; and (c) provided instructional feedback with student collaboration for problem solving and solution. Findings indicate that a focus on CSI may help facilitate WPS skills developing for ELs at risk of mathematics-learning difficulties (MLD). Educator preparation recommendations are embedded throughout with implications for future research and practice also discussed.
Computational cavitating viscous liquid flows in a pump as turbine and Reynolds number effects
Authors: Li Wen-Guang , Zhang Yu-Liang
Published: May 2018

Cavitating flows of viscous oils in an experimental centrifugal pump with low specific speed are modeled and simulated by using the time-averaged Navier–Stokes equations and standard [Formula: see text] turbulence model as well as full cavitation model based on the computational fluid dynamics method, when the pump operates in the reverse direction as turbine to generate power. The cavitation characteristics are identified at part-load, best efficiency and over-load points and five viscosities. Effects of viscosity on net positive suction head required are clarified. Net positive suction head required correction factor and conversion factor curves are obtained and correlated to impeller Reynolds number. The flow and cavitation models are validated with the existing experimental results and empirical correlations. Pressure and helix angle profiles at the draft tube entrance, cavity shape, swirling flow pattern in the draft tube, and the pressure coefficient distribution over the blade surfaces are presented. The presented results can be useful for design, selection, performance prediction, and impeller redesign of a pump as turbine.
Evidence of Serial Processing in Visual Word Recognition
Authors: White Alex L. , Palmer John , Boynton Geoffrey M.
Published: May 2018

To test the limits of parallel processing in vision, we investigated whether people can recognize two words at once. Participants viewed brief, masked pairs of words and were instructed in advance to judge both of the words (dual-task condition) or just one of the words (single-task condition). For judgments of semantic category, the dual-task deficit was so large that it supported all-or-none serial processing: Participants could recognize only one word and had to guess about the other. Moreover, participants were more likely to be correct about one word if they were incorrect about the other, which also supports a serial-processing model. In contrast, judgments of text color with identical stimuli were consistent with unlimited-capacity parallel processing. Thus, under these conditions, serial processing is necessary to judge the meaning of words but not their physical features. Understanding the implications of this result for natural reading will require further investigation.
Knowledge sharing and organizational change: Practice interactions in Australian local government
Authors: Leith Dean , Yerbury Hilary
Published: May 2018

The sharing of knowledge in organizations is deemed critical to achieving environmental and economic sustainability outcomes. This study applies a practice theoretical approach to investigating knowledge sharing in a team in local government created to break down the boundaries which have led to siloed practices. Findings indicate a range of activities, including influencing and resisting, and these differ from findings in other studies. Analysis of organizational discourses, physical arrangements and social spaces of organizations demonstrated the existence of two distinct practices: knowledge sharing and organizational change. Sharing knowledge of the organization and its ways of working were found to be as important as sharing subject knowledge and expertise.
Health information seeking, beliefs about abilities, and health behaviour among Finnish seniors
Authors: Eriksson-Backa Kristina , Enwald Heidi , Hirvonen Noora , Huvila Isto
Published: May 2018

The paper presents a study that examines older Finnish adults’ self-perceived capability to access, evaluate, understand and use health-related information, and their perceived ability to influence their health themselves, and the relationship between these factors and their current health, health behaviour and information seeking. Questionnaires were mailed by post to 1000 Finns aged 65–79 years, and a total of 281 completed questionnaires (28%) were returned. Of these, 273 were included in the study. Cross-tabulation and chi-square tests were used for the analysis. Results showed that both a stronger belief in one’s capability to master health information and to act in a healthy manner were positively linked to better health and health behaviour as well as more active information behaviour. These beliefs can be important factors for influencing certain health behaviours and even behaviour change.
Factors of the epidemiological triad that influence the persistence of human papilloma virus infection in women with systemic lupus erythematosus
Authors: Méndez-Martínez S , García-Carrasco M , Jiménez-Herrera E A , Mendoza-Pinto C , Etchegaray-Morales I , Barahona-Rubio P W , Gálvez-Romero J L , Munguía-Realpozo P , Muñóz-Guarneros C O , Cedillo-Ramírez M L , Silva-Gómez S E , Linares-Fleites G , Rojas-Vallaraga A
Published: May 2018

We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.