bluuebunny/crossref_metadata_2025 huggingface dataset:
In the setting of β-cell stress, the pancreatic duct gland transcriptome shows characteristics of an activated regenerative response
Authors: Butler Alexandra E. , Kirakossian David , Gurlo Tatyana , Gao Fuying , Coppola Giovanni , Butler Peter C.
Published: August 2018

The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche based on its coiled tubular structure embedded in mesenchyme, its proliferation and expansion in response to pancreatic injury, and the fact that it contains endocrine and exocrine epithelial cells. Little is known of the molecular signature of the PDG compartment in either a quiescent state or the potentially activated state during β-cell stress characteristic of diabetes. To address this, we performed RNA sequencing on RNA obtained from PDGs of wild-type vs. prediabetic HIP rats, a model of type 2 diabetes. The transcriptome of the PDG compartment, compared with a library of 84 tissue types, placed PDGs midpoint between the exocrine and endocrine pancreas and closely related to seminiferous tubules, consistent with a role as a stem cell niche for the exocrine and endocrine pancreas. Standard differential expression analysis (permissive threshold P < 0.005) identified 245 genes differentially expressed in PDGs from HIP rats vs. WT rats, with overrepresentation of transcripts involved in acute inflammatory responses, regulation of cell proliferation, and tissue development, while pathway analysis pointed to enrichment of cell movement-related pathways. In conclusion, the transcriptome of the PDG compartment is consistent with a pancreatic stem cell niche that is activated by ongoing β-cell stress signals. The documented PDG transcriptome provides potential candidates to be exploited for lineage tracing studies of this as yet little investigated compartment.

NEW & NOTEWORTHY The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche. Transcriptome analysis of the PDG gland placed it midpoint between exocrine and endocrine tissues with adaptation toward response to inflammation and increased cell movement in a model of type 2 diabetes with ongoing β-cell apoptosis. These findings support the proposal that PDGs may act as a pancreatic stem cell niche.
Endotoxemia-enhanced renal vascular reactivity to endothelin-1 in cirrhotic rats
Authors: Chuang Chiao-Lin , Chang Ching-Chih , Hsu Shao-Jung , Huang Hui-Chun , Lee Fa-Yauh , Huang Ling-Ju , Lee Shou-Dong
Published: August 2018

Hepatorenal syndrome (HRS), a severe complication of advanced cirrhosis, is defined as hypoperfusion of kidneys resulting from intense renal vasoconstriction in response to generalized systemic arterial vasodilatation. Nevertheless, the mechanisms have been barely investigated. Cumulative studies demonstrated renal vasodilatation in portal hypertensive and compensated cirrhotic rats. Previously, we identified that blunted renal vascular reactivity of portal hypertensive rats was reversed after lipopolysaccharide (LPS). This study was therefore conducted to delineate the sequence of renal vascular alternation and underlying mechanisms in LPS-treated cirrhotic rats. Sprague-Dawley rats were randomly allocated to receive sham surgery (Sham) or common bile duct ligation (CBDL). LPS was induced on the 28th day after surgery. Kidney perfusion was performed at 0.5 or 3 h after LPS to evaluate renal vascular response to endothelin-1 (ET-1). Endotoxemia increased serum ET-1 levels ( P < 0.0001) and renal arterial blood flow ( P < 0.05) in both Sham and CBDL rats. CBDL rats showed enhanced renal vascular reactivity to ET-1 at 3 h after LPS ( P = 0.026). Pretreatment with endothelin receptor type A (ETA) antagonist abrogated the LPS-enhanced renal vascular response in CBDL rats ( P < 0.001). There were significantly lower inducible nitric oxide synthase (iNOS) expression but higher ETAand phosphorylated extracellular signal-regulated kinase (p-ERK) expressions in renal medulla of endotoxemic CBDL rats ( P < 0.05). We concluded that LPS-induced renal iNOS inhibition, ETAupregulation, and subsequent ERK signaling activation may participate in renal vascular hyperreactivity in cirrhosis. ET-1-targeted therapy may be feasible in the control of HRS.

NEW & NOTEWORTHY Hepatorenal syndrome (HRS) occurred in advanced cirrhosis after large-volume paracentesis or bacterial peritonitis. We demonstrated that intraperitoneal lipopolysaccharide (LPS) enhanced renal vascular reactivity to endothelin-1 (ET-1) in cirrhotic rats, accompanied by inducible nitric oxide synthase inhibition, endothelin receptor type A (ETA) upregulation, and subsequent extracellular signal-regulated kinase activation in renal medulla. Pretreatment with ETAantagonist abrogated the LPS-enhanced renal vascular response in common bile duct ligation rats. These findings suggest that further clinical investigation of ET-1-targeted therapy may be feasible in the control of HRS.
Antibodies aggravate the development of ischemic heart failure
Authors: Keppner Lea , Heinrichs Margarete , Rieckmann Max , Demengeot Jocelyne , Frantz Stefan , Hofmann Ulrich , Ramos Gustavo
Published: August 2018

Heart-specific antibodies have been widely associated with myocardial infarction (MI). However, it remains unclear whether autoantibodies mediate disease progression or are a byproduct of cardiac injury. To disambiguate the role of immunoglobulins in MI, we characterized the development of ischemic heart failure in agammaglobulinemic mice (AID−/−μS−/−). Although these animals can produce functional B cells, they cannot synthesize secretory IgM (μS−/−) or perform Ig class switching (AID−/−), leading to complete antibody deficiency. Agammaglobulinemia did not affect overall post-MI survival but resulted in a significant reduction in infarct size. Echocardiographic analyses showed that, compared with wild-type infarcted control mice, AID−/−μS−/− mice exhibited improved cardiac function and reduced remodeling on day 56 post-MI. These differences remained significant even after animals with matched infarct sizes were compared. Infarcted AID−/−μS−/− mice also showed reduced myocardial expression levels of transcripts known to promote adverse remodeling, such as matrix metalloproteinase-9, collagen type I a1, collagen type III a1, and IL-6. An unbiased screening of the heart reactivity potential in the plasma of wild-type MI animals revealed the presence of antibodies that target the myocardial scar and collagenase-sensitive epitopes. Moreover, we found that IgG accumulated within the scar tissues of infarcted mice and remained in close proximity with cells expressing Fcγ receptors (CD16/32), suggesting the existence of an in situ IgG-Fcγ receptor axis. Collectively, our study results confirm that antibodies contribute to ischemic heart failure progression and provide novel insights into the mechanisms underlying this phenomenon.

NEW & NOTEWORTHY Our study sheds some light on the long-standing debate over the relevance of autoantibodies in heart failure and might stimulate future research in the field. The observation of extracellular matrix-specific antibodies and the detection of Fcγ receptor-expressing cells within the scar provide novel insights into the mechanisms by which antibodies may contribute to adverse remodeling.
Multilayer flow modulator enhances vital organ perfusion in patients with type B aortic dissection
Authors: Rikhtegar Nezami Farhad , Athanasiou Lambros S. , Amrute Junedh M. , Edelman Elazer R.
Published: August 2018

Management of aortic dissections (AD) is still challenging, with no universally approved guideline among possible surgical, endovascular, or medical therapies. Approximately 25% of patients with AD suffer postintervention malperfusion syndrome or hemodynamic instability, with the risk of sudden death if left untreated. Part of the issue is that vascular implants may themselves induce flow disturbances that critically impact vital organs. A multilayer mesh construct might obviate the induced flow disturbances, and it is this concept we investigated. We used preintervention and post-multilayer flow modulator implantation (PM) geometries from clinical cases of type B AD. In-house semiautomatic segmentation routines were applied to computed tomography images to reconstruct the lumen. The device was numerically reconstructed and adapted to the PM geometry concentrically fit to the true lumen centerline. We also numerically designed a pseudohealthy case, where the geometry of the aorta was extracted interpolating geometric features of preintervention, postimplantation, and published representative healthy volunteers. Computational fluid dynamics methods were used to study the time-dependent flow patterns, shear stress metrics, and perfusion to vital organs. A three-element Windkessel lumped parameter module was coupled to a finite-volume solver to assign dynamic outlet boundary conditions. Multilayer flow modulator not only significantly reduced false lumen blood flow, eliminated local flow disturbances, and globally regulated wall shear stress distribution but also maintained physiological perfusion to peripheral vital organs. We propose further investigation to focus the management of AD on both modulation of blood flow and restoration of physiologic end-organ perfusion rather than mere restoration of vascular lamina morphology.

NEW & NOTEWORTHY The majority of aortic dissection modeling efforts have focused on the maintenance of physiological flow using minimally invasive placed grafts. The multilayer flow modulator is a complex mesh construct of wires, designed to eliminate flow disruptions in the lumen, regulate the physiological wall stresses, and enhance endothelial function and offering the promise of improved perfusion of vital organs. This has never been fully proved or modeled, and these issues we confirmed using a dynamic framework of time-varying arterial waveforms.
Disparate effects of antibiotics on hypertension
Authors: Galla S. , Chakraborty S. , Cheng X. , Yeo J. , Mell B. , Zhang H. , Mathew A. V. , Vijay-Kumar M. , Joe B.
Published: August 2018

Gut microbiota are associated with a variety of complex polygenic diseases. The usage of broad-spectrum antibiotics by patients affected by such diseases is an important environmental factor to consider, because antibiotics, which are widely prescribed to curb pathological bacterial infections, also indiscriminately eliminate gut commensal microbiota. However, the extent to which antibiotics reshape gut microbiota and per se contribute to these complex diseases is understudied. Because genetics play an important role in predisposing individuals to these modern diseases, we hypothesize that the extent to which antibiotics influence complex diseases depends on the host genome and metagenome. The current study tests this hypothesis in the context of hypertension, which is a serious risk factor for cardiovascular diseases. A 3 × 2 factorial design was used to test the blood pressure (BP) and microbiotal effects of three different antibiotics, neomycin, minocycline, and vancomycin, on two well-known, preclinical, genetic models of hypertension, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), both of which develop hypertension, but for different genetic reasons. Regardless of the class, oral administration of antibiotics increased systolic blood pressure of the S rat, while minocycline and vancomycin, but not neomycin, lowered systolic blood pressure in the SHR. These disparate BP effects were accompanied by significant alterations in gut microbiota. Our study highlights the need to consider an individualized approach for the usage of antibiotics among hypertensives, as their BP could be affected differentially based on their individual genetic and microbiotal communities.
FLYWCH1, a Novel Suppressor of Nuclear β-Catenin, Regulates Migration and Morphology in Colorectal Cancer
Authors: Muhammad Belal A. , Almozyan Sheema , Babaei-Jadidi Roya , Onyido Emenike K. , Saadeddin Anas , Kashfi Seyed Hossein , Spencer-Dene Bradley , Ilyas Mohammad , Lourdusamy Anbarasu , Behrens Axel , Nateri Abdolrahman S.
Published: August 2018

Wnt/β-catenin signaling plays a critical role during development of both normal and malignant colorectal cancer tissues. Phosphorylation of β-catenin protein alters its trafficking and function. Such conventional allosteric regulation usually involves a highly specialized set of molecular interactions, which may specifically turn on a particular cell phenotype. This study identifies a novel transcription modulator with an FLYWCH/Zn-finger DNA-binding domain, called “FLYWCH1.” Using a modified yeast-2-hybrid based Ras-Recruitment system, it is demonstrated that FLYWCH1 directly binds to unphosphorylated (nuclear) β-catenin efficiently suppressing the transcriptional activity of Wnt/β-catenin signaling that cannot be rescued by TCF4. FLYWCH1 rearranges the transcriptional activity of β-catenin/TCF4 to selectively block the expression of specific downstream genes associated with colorectal cancer cell migration and morphology, including ZEB1, EPHA4, and E-cadherin. Accordingly, overexpression of FLYWCH1 reduces cell motility and increases cell attachment. The expression of FLYWCH1 negatively correlates with the expression level of ZEB1 and EPHA4 in normal versus primary and metastatic colorectal cancer tissues in patients. Thus, FLYWCH1 antagonizes β-catenin/TCF4 signaling during cell polarity/migration in colorectal cancer.

Implications:

This study uncovers a new molecular mechanism by which FLYWCH1 with a possible tumor suppressive role represses β-catenin-induced ZEB1 and increases cadherin-mediated cell attachment preventing colorectal cancer metastasis.
Icariin Improves Sepsis-Induced Mortality and Acute Kidney Injury
Authors: Xie Chaoyang , Liu Lei , Wang Zhigang , Xie Hongchang , Feng Yonghua , Suo Jingjun , Wang Menghao , Shang Wenjun , Feng Guiwen
Published: August 2018

Objectives: Icariin (ICA) is a bioactive flavonoid with renal protective actions. This study investigated the effects of ICA on renal injury, inflammation, oxidative damage, apoptosis, and survival in a mouse model of cecal ligation and perforation (CLP)-induced sepsis. Methods: Sepsis was induced by CLP. Mice were treated with ICA (30 or 60 mg/kg) for 3 days before CLP. Renal functions, inflammatory responses, oxidative damage, histological changes, apoptosis, and vascular permeability were examined. The effects of ICA on CLP-induced expression of renal nuclear factor-κB (NF-κB), cleaved caspase-3, Bax, and Bcl-2 were evaluated. Results: Mice in the CLP group had a low survival rate and increases in blood urea nitrogen and creatinine levels, proinflammatory cytokine levels, oxidative damage, apoptosis, and vascular permeability. These renal changes were dramatically improved by ICA treatment, especially in the 60 mg/kg ICA group. The detection of molecules involved in the inflammation and apoptosis of the kidney indicated that ICA reduced expression of NF-κB, cleaved caspase-3, and Bax but enhanced expression of Bcl-2. Conclusion: ICA improves CLP-induced mortality and acute kidney injury by inhibiting renal oxidant damage, inflammatory responses, apoptosis, and vascular permeability.
Human Paleoneurology and the Evolution of the Parietal Cortex
Authors: Bruner Emiliano
Published: August 2018

Paleoneurology deals with the study of brain anatomy in fossil species, as inferred from the morphology of their endocranial features. When compared with other living and extinct hominids, Homo sapiens is characterized by larger parietal bones and, according to the paleoneurological evidence, also by larger parietal lobes. The dorsal elements of the posterior parietal cortex (superior parietal lobules, precuneus, and intraparietal sulcus) may be involved in these morphological changes. This parietal expansion was also associated with an increase in the corresponding vascular networks, and possibly with increased heat loads. Only H. sapiens has a specific early ontogenetic stage in which brain form achieves such globular appearance. In adult modern humans, the precuneus displays remarkable variation, being largely responsible for the longitudinal parietal size. The precuneus is also much more expanded in modern humans than in chimpanzees. Parietal expansion is not influenced by brain size in fossil hominids or living primates. Therefore, our larger parietal cortex must be interpreted as a derived feature. Spatial models suggest that the dorsal and anterior areas of the precuneus might be involved in these derived morphological variations. These areas are crucial for visuospatial integration, and are sensitive to both genetic and environmental influences. This article reviews almost 20 years of my collaborations on human parietal lobe evolution, integrating functional craniology, paleoneurology, and evolutionary neuroanatomy.
Care Pathway Effect on In-Hospital Care for ST-Elevation Myocardial Infarction
Authors: Aeyels Daan , Bruyneel Luk , Sinnaeve Peter R. , Claeys Marc J. , Gevaert Sofie , Schoors Danny , Panella Massimiliano , Sermeus Walter , Vanhaecht Kris
Published: August 2018

Objectives: To study the care pathway effect on the percentage of patients with ST-elevation myocardial infarction ­(STEMI) receiving timely coronary reperfusion and the percentage of STEMI patients receiving optimal secondary prevention. Methods: A care pathway was implemented by the Collaborative Model for Achieving Breakthrough Improvement. One pre-intervention and 2 post-intervention audits included all adult STEMI patients admitted within 24 h after onset and eligible for reperfusion. Adjusted (hospital random intercepts and controls for transfer and out-of-office admission) differences in composite outcomes were analyzed by a multilevel logistic regression. Results: Significant improvements in intervals between the first medical contact (FMC) to percutaneous coronary intervention (PCI) and between the door to PCI were shown between post-intervention audit II and post-intervention audit I. Secondary prevention significantly deteriorated at post-intervention audit I but improved significantly between both post-intervention audits. Six out of nine outcomes were significantly poorer in the case of transfer. The interval from FMC to PCI was significantly poorer for patients admitted during out-of-office hours. Conclusions: After care pathway implementation, composite outcomes improved for in-hospital STEMI care. Collaborative efforts exploited heterogeneity in performance between hospitals. Iterative and incremental care pathway implementation maximized performance improvement.
The Utility of Feticide Procedure to Shorten the Induction-to-Abortion Interval in Medical Abortion
Authors: Akkurt Mehmet Ozgur , Akkurt Iltac , Yavuz And , Yalcin Serenat Eris , Coskun Bora , Sezik Mekin
Published: August 2018

Aim: To evaluate the effect of intracardiac potassium chloride feticide procedure (FP) on the induction-to-abortion (I-to-A) interval for various indications in the termination of pregnancy. Method: Medically indicated abortions between 17 and 28 weeks’ gestation were retrospectively evaluated and allocated into 2 groups: Cases with (group 1, n = 58) or without an FP (group 2, n = 60). I-to-A intervals were compared across the groups, considering different baseline parameters and fetal abnormality categories. Results: There were no differences among the groups except in gestational age (GA; mean, 21.2 vs. 19.6 weeks, p = 0.01) in group 1. Overall, the I-to-A interval was shorter (900 ± 233 vs. 1,198 ± 375 min, p = 0.001) and prolonged medical abortion (I-to-A interval > 48 h) was less common (2% vs. 6%, p = 0.03) in group 1. The facilitating effect of FP persisted when indications were categorized as central nervous system, chromosomal, other structural abnormalities, and unclassified conditions. Logistic regression analyses demonstrated the following features to be associated with expulsion of fetus after 24-h: (1) advanced GA (> 24 week; aOR 6.9, 95% CI 3.24–14.72), (2) central nervous system abnormalities (aOR 5.3, 95% CI 2.6–11.4), (3) lack of feticide (aOR 3.67, 95% CI 2.24–10.72). Conclusion: FPs seem to shorten the I-to-A interval and decrease prolonged I-to-A interval rates. This facilitating effect remains unchanged for various medical indications.
MicroRNA-124 Prevents H2O2-Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway
Authors: Gu Xiu-li
Published: August 2018

Aim: To investigate the regulation of microRNA-124 ­(miRNA-124) on NF-κB pathway from H2O2-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC). Methods: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to detect hLEC ­viability. HLECs were divided into Blank, H2O2, mimics (miRNA-124 mimics) + H2O2, NC+ H2O2, pyrrolidine dithiocarbamate (PDTC; NF-κB signaling pathway inhibitor) + H2O2, and inhibitors (miRNA-124 inhibitors) + PDTC + H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1. Results: The H2O2-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H2O2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H2O2-induced hLEC. Conclusion: MiRNA-124 prevents H2O2-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-κB pathway.
Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal Insufficiency
Authors: Hanna Ramy M. , Selamet Umut , Bui Patrick , Sun Shih-Fan , Shenouda Olivia , Nobakht Niloofar , Barsoum Marina , Arman Farid , Rastogi Anjay
Published: August 2018

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.
Cardiac Magnetic Resonance Evaluation of the Extent of Myocardial Injury in Patients with Inferior ST Elevation Myocardial Infarction and Concomitant ST Depression in Leads V1–V3: Analysis from the MITOCARE Study
Authors: Jia Xiaoming , Heiberg Einar  , Sejersten Ripa Maria , Engblom Henrik , Carlsson Marcus , Halvorsen Sigrun , Arheden Håkan , Atar Dan , Clemmensen Peter , Birnbaum Yochai
Published: August 2018

The aim of our study was to examine the pathophysiology of ST depression (STD) in leads V1–V3 in the setting of inferior ST elevation myocardial infarction (iSTEMI) through the perspective of cardiac magnetic resonance (CMR). Methods: Differences in myocardial area at risk (MaR), infarct size, ejection fraction and myocardial segment involvement by CMR were compared in MITOCARE trial patients with first iSTEMI with ST elevation (STE), STD or no ST changes (NST) in V1–V3. The frontal plane projection of the inferior wall MaR in relationship to the anterior/posterior chest wall was calculated and compared between groups. Results: Fifty-six patients were included. Patients with STD (n = 38) and STE (n = 5) in V1–V3 had significantly larger mean MaR compared to NST (n = 13; 32 ± 7%LV, 36 ± 10%LV and 26 ± 6%LV, respectively; p = 0.01). STD in leads V1–V3 was associated with more apical inferior and mid inferoseptal involvement and had a larger mean frontal plane projection of MaR compared with NST (24 ± 6%LV vs. 20 ± 6%LV, p = 0.04). Conclusion: STD in V1–V3 in iSTEMI is associated with larger MaR, more extension into the inferoseptal segments and likely results from greater frontal plane projection of the MaR, leading to reciprocal changes on the electrocardiogram.
Once-a-Day Trazodone in the Treatment of Depression in Routine Clinical Practice
Authors: Češková Eva , Šedová Michaela , Kellnerová Renata , Starobová Olga
Published: August 2018

Objective: The aim of the study was to evaluate the efficacy, tolerability, and safety of once-a day trazodone tablets (Trittico Prolong® 300 mg) in patients with moderate to severe depression in routine clinical practice. Methods: Men and women ≥18 years old with Montgomery-Åsberg Depression Rating Scale (MADRS) scores > 21 and Clinical Global Impression – Severity (CGI/S) ≥4 were included in this post-authorization, non-interventional, observational prospective safety study, conducted in 8 psychiatric centers in the Czech ­Republic. The acute treatment phase lasted 5 weeks: 1 week of titration and 4 weeks of full-dose treatment. Patients had follow-up visits 9 and 21 weeks after commencing ­treatment. Results: Overall, 85 patients were enrolled in the study, of which 80 completed the acute treatment of 5 weeks. There were significant decreases in the overall MADRS score from the baseline mean value of 27.4–21.2 at week 1 (p < 0.001), and a further decrease to 7.9 at week 5 (p < 0.001). The severity of depression according to CGI/S gradually declined. Most patients reported improvement after 6 days of trazodone treatment. The most frequent adverse drug reactions (ADRs) reported were somnolence and fatigue. Conclusions: Trazodone, in the new extended-release formulation, had very good effects in clinical practice, both in previously untreated depressive episodes and in episodes not responsive to previous antidepressive therapy.
Profiles and Bioinformatics Analysis of Differentially Expressed Circrnas in Taxol-Resistant Non-Small Cell Lung Cancer Cells
Authors: Xu Ning , Chen Shaomu , Liu Yufeng , Li Wei , Liu Zeyi , Bian Xiaojie , Ling Chunhua , Jiang Min
Published: August 2018

Background/Aims: Circular RNAs (circRNAs) act as microRNA (miRNA) sponges that regulate gene expression and are involved in physiological and pathological processes. In this study, we evaluated the roles of circRNAs in the chemoresistance of non-small cell lung cancer (NSCLC) to taxol. Methods: High-throughput circRNA microarrays were employed to investigate the circRNA profiles of parental A549 and taxol-resistant A549/Taxol cells. We predicted the miRNA targets of differentially expressed circRNAs via miRNA prediction software and then constructed a circRNA/miRNA network using Cytoscape. Bioinformatics analyses were performed to annotate dysregulated circRNAs in detail. Results: We detected 2909 significantly upregulated and 8372 downregulated circRNAs in A549/Taxol cells compared with A549 cells. The circRNA/miRNA network displayed their interactions, suggesting that circRNAs exert biological effects by absorbing and sequestering miRNA molecules. Computational Gene Ontology and pathway analyses were used to determine the biological function and signaling pathways of host genes of dysregulated circRNAs and to identify potential molecular mechanisms prompting the resistance of NSCLC to taxol. Conclusion: This study focusing on circRNAs related to taxol resistance provides a basis for clarifying the development and progression of drug resistance and for identifying therapeutic targets in NSCLC.
The Association of Urinary Sodium and Potassium with Renal Uric Acid Excretion in Patients with Chronic Kidney Disease
Authors: Li Fengqin , Guo Hui , Zou Jianan , Chen Weijun , Lu Yijun , Zhang Xiaoli , Fu Chensheng , Xiao Jing , Ye Zhibin
Published: August 2018

Background/Aims: Hypertension and hyperuricemia are closely associated with an intermingled cause and effect relationship. Additionally, urinary sodium and potassium excretion is related to blood pressure. Whether or not it is associated with urinary uric acid excretion is not clear. Therefore, we aim to study the association of urinary sodium and potassium with renal uric acid excretion in patients with CKD. Methods: A cross-sectional study of 428 patients with CKD recruited from our department was conducted. All patients were divided into hypertension and non-hypertension group. In these two groups, Spearman correlation and multiple linear regression analysis were used to study the correlation of urinary sodium and potassium with renal handling of uric acid. Results: According to multiple linear regression analysis, in hypertension group, fractional excretion of sodium (FEna) was negatively correlated with 24 hour urinary uric acid (24-hUur) and uric acid clearance rate (Cur) (beta coefficients [B]=-0.066, -0.182, respectively; both P< 0.05), and positively correlated with fractional excretion of uric acid (FEur) (B=1.641, P< 0.001). Additionally, fractional excretion of potassium (FEk) was positively correlated with FEur (B=0.576, P< 0.001), but not related to 24-hUur and Cur (both P>0.05). And urinary sodium/potassium ratio (Una/k) was negatively related to 24-h Uur and Cur (B=-0.047, -0.159, both P< 0.05), and positively related to FEur (B=0.578, P< 0.05). Furthermore, FEna and FEk was still positively related to FEur in the lowest tertile of eGFR groups (both P< 0.05), but not related in the second and highest tertile of eGFR groups (all P> 0.05). In non-hypertension group, FEna was negatively correlated with 24-hUur (B=-0.589, P< 0.05), but not related to Cur and FEur (both P> 0.05). both FEk and Una/k was not related to 24-h Uur, Cur and FEur (all P> 0.05). Moreover, FEna and FEk was still not correlated with FEur in all tertiles of eGFR groups (all P> 0.05). Conclusion: We found that in patients with CKD, urinary sodium and potassium excretion is closely correlated to renal handling of uric acid, which was pronounced in hypertensive patients with low eGFR. This phenomenon may be one of the mechanisms of the relationship between hypertension and hyperuricemia. Further research is needed to confirm it. It is expected to manage hyperuricemia in terms of controlling the diet of sodium and potassium.
Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area
Authors: Zizzo Carmela , Testa Alessandra , Colomba Paolo , Postorino Maurizio , Natale Giuseppe , Pini Alessandro , Francofonte Daniele , Cammarata Giuseppe , Scalia Simone , Sciarrino Serafina , Zoccali Carmine , Duro Giovanni
Published: August 2018

Background/Aims: Fabry disease (FD) is a lysosomal storage disorder characterized by pervasive renal involvement. However, this disease is underdiagnosed in patient with chronic kidney disease (CKD), including those with end stage renal disease (ESRD), so their investigation represents an unexploited opportunity for early diagnosis of the disease and for its identification in relatives of affected patients. Methods: We investigated Fabry disease in a clinical and biological database including ESRD patients of unknown cause in a geographical area with 2 million residents. The study was based on state of art GLA gene sequencing and was extended to relatives of affected ESRD patients. Results: Among ESRD patients qualified for enrollment into this study, a previously undiagnosed young man harboring the mutation p.I91T was identified. The study of the proband's family led to the identification of 8 additional cases. In another ESRD male patient, we identified the functional polymorphism p.D313Y. Furthermore, in 55 ESRD patients (24.2%) we found intronic polymorphisms of uncertain functional relevance in the non-coding regions of the GLA gene. Conclusion: A comprehensive survey of ESRD patients in a geographical area of 2 million residents identified one undiagnosed case of Fabry disease and led to the identification of 8 additional cases among his relatives. Screening protocols starting from the dialysis population and upstream extended to families of affected individuals may be an effective strategy to maximize the early identification of subjects with Fabry disease.
Association of Peridialysis Blood Pressure and Its Variability with Cardiovascular Events in Hemodialysis Patients
Authors: Liao Ruoxi , Li Jiameng , Xiong Yuqin , Lin Liping , Wang Liya , Sun Si , Su Baihai
Published: August 2018

Background/Aims: Blood pressure variability (BPV) is a novel cardiovascular risk factor for the population undergoing hemodialysis (HD). Methods: We conducted a retrospective cohort study of 526 HD patients. Four short-term peridialysis BPV metrics were analyzed: systolic blood pressure (SBP) change, SBP coefficient of variation (CV), SBP intradialytic average real variability (ARV), and absolute SBP residual. Multi variate analysis with Cox regression models were used to account for the potential confounders. Results: Short-term BPV is found to be affected by age, pre-dialysis SBP, antihypertensive drugs, dialysis time, and vascular access. Calcium-channel blockers (CCBs) were found to be associated with lower BPV than those on non-CCB therapy or no antihypertensive drugs. Patients dialyzed in the morning had a greater absolute SBP change than those dialyzed in the afternoon or evening. Patients using fistulas had a lower BPV than catheters. Higher BPV metrics including SBP CV (unadjusted hazard ratio [HR]: 1.37, 95% confidence interval [CI] 1.14-1.66, p=0.001), SBP intradialytic ARV (unadjusted HR: 1.46, 95% CI: 1.20-1.77, p< 0.001), and SBP residual (unadjusted HR: 1.47, 95% CI: 1.21-1.79, p< 0.001) were associated with a greater risk of cardiovascular events. After complete multivariate adjustment for other potential confounders, the HR remained statistically significant for SBP intradialytic ARV (HR 1.31, 95% CI: 1.04-1.66, p=0.024). Conclusion: Peridialytic BPV may be a potential target for improved blood pressure (BP) management in HD patients. Each short-term BPV metric has different advantages and disadvantages and should be applied according to the clinical context and purpose.
Inhabitat: An Imaginary Ecosystem in a Children’s Science Museum
Authors: Ji Haru Hyunkyung , Wakefield Graham
Published: August 2018

Inhabitat is a mixed-reality artwork in which participants become part of an imaginary ecology through three simultaneous perspectives of scale and agency; three distinct ways to see with other eyes. This imaginary world was exhibited at a children’s science museum for five months, using an interactive projection-augmented sculpture, a large screen and speaker array, and a virtual reality head-mounted display. This paper documents the work’s motivations and design contributions, along with accounts of visitors’ playful engagements and reflections within the complex interconnectivity of an artificial nature.
Diastrophisms: Visual and Sound Assembly in Remembrance of an Earthquake
Authors: L’Huillier Nicole , Montero Valentina
Published: August 2018

Diastrophisms is a sound installation with a modular system that sends images through rhythmic patterns. It is built on a set of debris from the Alto Río building that was destroyed by the 27F earthquake in 2010 in Chile. Diastrophisms explores poetical, critical and political crossings between technology and matter in order to raise questions about the relationship between human beings and nature, to consider the construction of memory in a community by questioning the notion of monument, and to imagine new forms of communication in times of crisis.
Digital Heritage: Bringing New Life to the Montreux Jazz Festival’s Audio-Visual Archives with Immersive Installations
Authors: Henchoz Nicolas , Crank Allison
Published: August 2018

To revive the Montreux Jazz Festival’s archival live-concert footage, three immersive installations were designed using three different principles of augmentation, physicality and interaction. The primary aim was to engage the user in a new relationship with digitized heritage. Audience observations indicated a strong emotional connection to the content, the artist and the crowd, as well as the development of new social interactions. Experimentation showed close interaction between the three principles, while the three installations suggested methodologies for reviving audio-visual archives.
Data Materialization: A Hybrid Process of Crafting a Teapot
Authors: Starrett Courtney , Reiser Susan , Pacio Tom
Published: August 2018

Data materialization is a workflow developed to create 3D objects from data-informed designs. Building upon traditional metalwork and craft, and new technology’s data visualization with generative art, this workflow expresses conceptually relevant data through 3D forms which are fabricated in traditional media. The process allows for the subtle application of data in visual art, allowing the aesthetic allure of the art object or installation to inspire intellectual intrigue. This paper describes the technical and creative process of Modern Dowry, a silver-plated 3D-print teapot on view at the Museum of the City of New York, June 2017–June 2018.
Knocking on the Door of Human-Animal Studies: Valuing Work Across Disciplinary and Species Borderlines
Authors: Hamilton Lindsay , Mitchell Laura
Published: August 2018

We argue that human-animal studies (HAS) literature is essential for theorizing work because it fosters a reflexive questioning of humanist power and a more sophisticated understanding of the co-dependency and co-creativity between the species. We highlight that the neglect of nonhuman animals in organization studies stems from a preoccupation with contemporary industrialization, human forms of rationality, and the mechanisms of capital exchange. Drawing upon the example of sheep and shepherding, we illustrate how a flexible approach to studying the value and worth of work is made possible by attending to other-than-human activity and value co-creation. We conclude by suggesting that the concept of work and its value needs a more species-inclusive approach to foster a less reductively anthropocentric canon of interdisciplinary scholarship in the field.
Joint Development of Offshore Oil and Gas Resources in the Arctic Ocean Region and the United Nations Convention on the Law of the Sea
Authors: Abrahamson John
Published: August 2018

The Arctic Ocean region presents certain challenges to peaceful cooperation between states, particularly in the locations where ocean boundaries and ownership of the related resources are disputed. The establishment of Joint Development Zones (JDZs) for the development of offshore oil and gas resources in the Arctic Ocean can facilitate international cooperation over resource development where there are competing claims. These claims are generally based on continental shelf jurisdiction under the provisions of the United Nations Convention on the Law of the Sea (UNCLOS). There are several alternative dispute resolution measures available underUNCLOS; however, a number of states have preferred to adopt aJDZas an interim measure to allow development. The significance ofJDZs for the Arctic Ocean region is that they can allow peaceful cooperation and development where the specific circumstances of Arctic claims make it difficult for the respective states to agree on the maritime boundary.
인지-인본주의적 정신 역동들 : Sidney Blatt의 이론적-철학적 업적 (Congnitive-Humanistic Psychodynamics : Sidney Blatt’s Theoretical-Philosophical Legacy)
Authors: Shahar Golan , Mayes Linda C.
Published: August 2018

( 초록 )

수많은 이론적-철학적 명제들이 Blatt의 광범위하고 탁월한 학문적 업적으로부터 나왔다. 그의 주요 연구 주제들은 (1) 인지, 특히 현실에 대한 마음의 지형도 혹은 표상; (2) 인본주의적인 요소들의 영향 (예컨데, 에이전시, 성장에 대한 열망, 게슈탈트, 균형 욕구 그리고 회복 탄력성); (3) 프로이트가 말한 역동적 무의식에 대한 끝없는 통찰, 이렇게 요약할 수 있을 것이다. 철학적 입장에서, Blatt은 ‘인지-인본주의적 정신역동’이라고 부를만한, 통합적 역량과 추종을 불허하는 업적들을 남겼다.
Infrared Spectroscopic Quantification of Methacrylation of Hyaluronic Acid: A Scaffold for Tissue Engineering Applications
Authors: Yousefi Farzad , Kandel Shital , Pleshko Nancy
Published: August 2018

Methacrylated hyaluronic acid (MeHA) has been used extensively in tissue engineering and drug delivery applications. The degree of methacrylation (DM) of HA impacts hydrogel crosslinking, which is of pivotal importance for cell interactions. The methacrylation reaction occurs over several hours, and DM is currently assessed post reaction and after dialysis of the solution, using nuclear magnetic resonance (1H NMR) data. Thus, there is little control over exact DM in a specific reaction. Here, infrared (IR) spectroscopy in attenuated total reflection (ATR) mode was investigated as an alternate modality for assessment of the DM of HA hydrogels, including during the reaction progression. Attenuated total reflection is a low-cost technique that is widely available in research and industry labs that can be used online during the reaction process. Strong correlations were achieved with IR-derived peak heights from dialyzed and lyophilized samples at 1708 cm−1 (from the methacrylic ester carbonyl vibration), and 1H NMR values ( R = 0.92, P = 6.56E-11). Additional IR peaks of importance were identified using principal component analysis and resulted in significant correlations with the 1H NMR DM parameter: 1454 cm−1 ( R = 0.85, P = 2.81E-8), 1300 cm−1 ( R = 0.95, P = 4.50E-14), 950 ( R = 0.85, P = 3.55E-8), 856 cm−1 ( R = 0.94, P = 1.20E-12), and 809 cm−1 ( R = 0.93, P = 3.54E-12). A multiple linear regression model to predict 1H NMR-derived DM using the 1708, 1300, and 1200 cm−1 peak heights as independent variables resulted in prediction with an error of 3.2% using dialyzed and lyophilized samples ( P < 0.001). Additionally, a multilinear regression model to predict the DM in undialyzed liquid MeHA samples obtained during the reaction process using similar peak height positions as independent variables resulted in a prediction error of 0.81% ( P < 0.05). Thus, IR spectroscopy can be utilized as an alternate modality to 1H NMR for quantification of the DM of MeHA while sampling either on-line during the methacrylation reaction as well as in post-lyophilized products. This could greatly simplify workflow for tissue engineering and other applications.
Pre-Citizenship in Walla Walla
Authors: Lacey W. A.
Published: August 2018

A large measure of self-government has been granted to the pupils of this high school, and they are learning valuable lessons in the essentials, of good citizenship. Various doubts about the workableness of such a system are here answered.
Student Responsibility in Evansville
Authors: Shrode Carl
Published: August 2018

“The essence of this plan, perhaps of any plan, lies in its spirit rather than in its technique,” the writer states. The plan which he offers has had a long period of trial and was recently given an overwhelming vote of approval by the faculty.
Spelling in the Junior High School
Authors: Forman W. O.
Published: August 2018

Is spelling in the Junior High School improving? What are its proper standards? Have good spellers disappeared with the faded glory of the spelling bee? The writer backs his answers with experience gathered in his school.
Some Problems of Today
Authors: Cousens John A.
Published: August 2018

Education must continually be made over to meet the requirements of each succeeding period of time, President Cousens reminds us. We have awakened in a strange country. With bewildering rapidity new life values are emerging.
Higher Degrees Not the Only Yardstick
Authors: Bray Willis Joseph
Published: August 2018

“The degree is a universally recognized measure of academic achievement, and this, supplemented by the character, professional training and experience of the prospective teacher, should be, and is rapidly becoming, the standard by which teachers are selected.”
Let's Outlaw Tongue-Lashings!
Authors: Myers Garry Cleveland
Published: August 2018

Ridicule and sarcasm are seen as a bullying attempt to crush pupil personalities.
Was Lincoln an Educated Man?
Authors: Clem Orlie
Published: August 2018

The author presents interesting evidence to show that Lincoln's estimate of his own attainments was far too modest.
Personality Challenges the Teacher
Authors: Copper Francis Roy
Published: August 2018

Have you a Linnaeus, a Disraeli, a Harper or a Vesalius in your classroom? One never knows!
Some Wealth Fallacies
Authors: Mead Lucia Ames
Published: August 2018

The public has much to learn about owning and earning, and about wise and beneficial spending.
An Aid to Understanding Japan
Authors: Graham D. F.
Published: August 2018

—and how, she used her schools to revolutionize her social order and exalt the Emperor.
Teachers' Colleges Not “Blind”
Authors: Slonim Ruth
Published: August 2018

A rejoinder to Supt. Hagie's article on Mediocrity in this magazine for April, 1940.
Four Marks of a Real Teacher
Authors: Chrisman Lewis H.
Published: August 2018

Rarely has the secret of what makes great and good teaching been so successfully caught and expressed as in this article.
A Pay-As-We-Go Building Program
Authors: Amidon P. S.
Published: August 2018

How a half-dozen new construction projects were handled without further mortgaging the future.
The Funny Side of Quizzes
Authors: Hodge C. Lewis
Published: August 2018

Countless gems of wisdom are to be found in students' answers. So why not enjoy correcting quizzes.
What is the Curriculum?
Authors: Eginton Daniel P.
Published: August 2018

Does it include selling newspapers, building a radio, and going to a dance? And should not the educational program be considered in its entirety?
The Denver Convention
Authors: Farley Belmont
Published: August 2018

Eightieth N.E.A. gathering considers the effects of the war upon education
A-Camping We Will Go!
Authors: Foster Dorothy R.
Published: August 2018

With a long-time, active interest in the outdoors, Dorothy R. Foster, seventh and eighth grade teacher in the Weeks Junior High School, Newton, Mass., is well-qualified to write on school camping trips. As a teacher of science and mathematics, she has taken a keen interest in coordinating the school-camp project each year and helped prepare the Newton Guide for Planning School Camping Trips.