bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective on Cholesterol Homeostasis: The Central Role of Scap
Authors: Brown Michael S. , Radhakrishnan Arun , Goldstein Joseph L.
Published: August 2017

Scap is a polytopic membrane protein that functions as a molecular machine to control the cholesterol content of membranes in mammalian cells. In the 21 years since our laboratory discovered Scap, we have learned how it binds sterol regulatory element-binding proteins (SREBPs) and transports them from the endoplasmic reticulum (ER) to the Golgi for proteolytic processing. Proteolysis releases the SREBP transcription factor domains, which enter the nucleus to promote cholesterol synthesis and uptake. When cholesterol in ER membranes exceeds a threshold, the sterol binds to Scap, triggering several conformational changes that prevent the Scap–SREBP complex from leaving the ER. As a result, SREBPs are no longer processed, cholesterol synthesis and uptake are repressed, and cholesterol homeostasis is restored. This review focuses on the four domains of Scap that undergo concerted conformational changes in response to cholesterol binding. The data provide a molecular mechanism for the control of lipids in cell membranes.
Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins
Authors: Schwingshackl Andreas , Lopez Benjamin , Teng Bin , Luellen Charlean , Lesage Florian , Belperio John , Olcese Riccardo , Waters Christopher M.
Published: August 2017

We previously proposed a role for the two-pore domain potassium (K2P) channel TREK-1 in hyperoxia (HO)-induced lung injury. To determine whether redundancy among the three TREK isoforms (TREK-1, TREK-2, and TRAAK) could protect from HO-induced injury, we now examined the effect of deletion of all three TREK isoforms in a clinically relevant scenario of prolonged HO exposure and mechanical ventilation (MV). We exposed WT and TREK-1/TREK-2/TRAAK-deficient [triple knockout (KO)] mice to either room air, 72-h HO, MV [high and low tidal volume (TV)], or a combination of HO + MV and measured quasistatic lung compliance, bronchoalveolar lavage (BAL) protein concentration, histologic lung injury scores (LIS), cellular apoptosis, and cytokine levels. We determined surfactant gene and protein expression and attempted to prevent HO-induced lung injury by prophylactically administering an exogenous surfactant (Curosurf). HO treatment increased lung injury in triple KO but not WT mice, including an elevated LIS, BAL protein concentration, and markers of apoptosis, decreased lung compliance, and a more proinflammatory cytokine phenotype. MV alone had no effect on lung injury markers. Exposure to HO + MV (low TV) further decreased lung compliance in triple KO but not WT mice, and HO + MV (high TV) was lethal for triple KO mice. In triple KO mice, the HO-induced lung injury was associated with decreased surfactant protein (SP) A and SPC but not SPB and SPD expression. However, these changes could not be explained by alterations in the transcription factors nuclear factor-1 (NF-1), NKX2.1/thyroid transcription factor-1 (TTF-1) or c-jun, or lamellar body levels. Prophylactic Curosurf administration did not improve lung injury scores or compliance in triple KO mice.
Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis
Authors: Xu Junwang , Zgheib Carlos , Hodges Maggie M. , Caskey Robert C. , Hu Junyi , Liechty Kenneth W.
Published: August 2017

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression.
Comparative Study of Two Cohorts of Newly Diagnosed Crohn's Disease Demonstrates Change in Therapeutic Strategies
Authors: Icht Oded , Yanai Henit , Ron Yulia , Rosner Guy , Yaron Ayala , Waizbard Amir , Ziv-Baran Tomer , Fishman Sigal , Dotan Iris
Published: August 2017

Background: There has been a paradigm shift in the treatment of Crohn's disease (CD) involving the rapid introduction of biologics and/or immunomodulators after diagnosis. We wished to assess whether this was applied to patients with newly diagnosed CD in a tertiary inflammatory bowel disease referral centre in Israel. Methods: Newly diagnosed CD patients were stratified into 2 groups: the early group was diagnosed between 2005 and 2007 and the late group was diagnosed between 2010 and 2012. Baseline demographics, medical and surgical treatments, disease course and complications during those 2 periods were analyzed. Results: Each group included 60 patients. Significantly higher rates of immunomodulators and biologics were administered to patients in the late group compared to the early group (81.7 and 36.7% compared to 56.7 and 18.3%, p = 0.004 and p = 0.021, respectively). On the other hand, steroid therapy was less prevalent in the late (36.7%) group compared to that of the early group (56.7%), p = 0.059. Medical and surgical CD outcomes, including exacerbations/hospitalizations and surgeries, were comparable for both groups. Conclusions: There was a change in treatment strategy between 2005-2007 and 2010-2012, as reflected in higher proportions of biologics/immunomodulators for patients with newly diagnosed CD. This was associated with a steroid-sparing effect.
Successful Use of Grenz Rays for Disseminated Superficial Actinic Porokeratosis: Report of 8 Cases
Authors: Ramelyte Egle , Bylaite-Bucinskiene Matilda , Dummer Reinhard , Imhof Laurence
Published: August 2017

Background: Disseminated superficial actinic porokeratosis (DSAP) is a rare keratinization disorder with potential malignant transformation, for which present treatment strategies show limited success. Aim: To evaluate the response of DSAP lesions to grenz ray radiotherapy (RTx). Methods: Data of patients treated with RTx at University Hospital Zurich, Switzerland, between 2004 and 2015, were reviewed. Patients with DSAP, who received at least 1 RTx treatment session and who had been followed up for at least 4 weeks were included in the further data analysis. Results: The study cohort consisted of 8 patients with a median age of 73 years (range 54-84). All were treated with grenz rays for DSAP. Most (7/8) patients showed complete clinical clearing of the lesions. All patients experienced temporary side effects of RTx, which resolved within 4 weeks after the last irradiation. Conclusion: We suggest radiotherapy with grenz rays as a treatment option for DSAP.
Behavioral Conditioning of Immune Responses with Cyclosporine A in a Murine Model of Experimental Autoimmune Uveitis
Authors: Bauer Dirk , Busch Martin , Pacheco-López Gustavo , Kasper Maren , Wildschütz Lena , Walscheid Karoline , Bähler Hanna , Schröder Minea , Thanos Solon , Schedlowski Manfred , Heiligenhaus Arnd
Published: August 2017

Objective: We examined the role of behavioral conditioning of immune responses with cyclosporine A (CsA) on the development of Th1/Th17-driven experimental autoimmune uveoretinitis (EAU). Methods: Mice received a 0.2% w/v saccharin solution as conditioned stimulus combined with CsA (20 mg/kg) in 6 association trials at 72-h intervals. For evocation periods, conditioned mice were reexposed to saccharin, whereas the conditioned but not reexposed group received water only. Animals were immunized with human interphotoreceptor-retinoid-binding protein peptide 161-180 (hIRBPp161-180) peptide in complete Freund adjuvant (CFA) and a concomitant injection of pertussis toxin. Results: In naïve mice subjected to the behavioral conditioning regimen, mitogen-induced interleukin (IL)-2 production was decreased in conditioned mice compared to conditioned but not reexposed animals. Incidence and severity of EAU were not significantly lower in behaviorally conditioned and immunized mice. ELISA analysis of splenocytes revealed a reduced interferon (IFN)-γ/IL-17 ratio in CsA-treated, conditioned but not reexposed, and conditioned animals. The adoptive transfer of antigen-specific splenocytes from animals behaviorally conditioned with CsA to naïve mice decreased the severity of EAU in recipient mice compared to the control group. In vitro activation of splenocytes isolated from immunized mice with agonists targeting TLR2 and NOD2 together with β2-adrenergic activation (induced by epinephrine, norepinephrine, or salbutamol) resulted in decreased IFN-γ but increased IL-17 immune responses. The β2-adrenergic antagonist propranolol could restore IFN-γ production, whereas only the norepinephrine-induced increase in IL-17 production was abrogated. Conclusions: We conclude that CsA conditioning in the EAU model mitigates Th1 but enhances Th17 immune responses, and does not ameliorate disease. The results imply that in EAU the mechanism of immune conditioning interacts with CFA components during active immunization, most likely via the TLR2/NOD2 pathway, and induces differentiation of Th17 cells that drive autoimmune diseases.
Progressive Kyphosis Associated with Tethered Cord Syndrome Treated by Posterior Vertebral Column Resection in a Pediatric Patient
Authors: Oktay Kadir , Ozsoy Kerem Mazhar , Gezercan Yurdal , Cetinalp Nuri Eralp , Erman Tahsin
Published: August 2017

Posterior vertebral column resection is a novel surgical approach for the treatment of progressive kyphosis associated with tethered cord syndrome that was first treated with untethering surgery. A patient with tethered cord syndrome associated with kyphosis first underwent untethering surgery, resulting in progressive kyphosis. Posterior vertebral column resection was performed to correct the kyphosis while shortening the spinal column to prevent the spinal cord from stretch injury. Good correction of kyphosis and reduction of tension on the neural elements were achieved without any neurological deficits. In progressive kyphosis associated with tethered cord syndrome, posterior vertebral column resection after untethering surgery represents a safe and efficacious but technically challenging option.
Role of Dynamic Contrast-Enhanced Perfusion Magnetic Resonance Imaging in Grading of Pediatric Brain Tumors on 3T
Authors: Gupta Pradeep Kumar , Saini Jitender , Sahoo Prativa , Patir Rana , Ahlawat Sunita , Beniwal Manish , Thennarasu Kandavel , Santosh Vani , Gupta Rakesh Kumar
Published: August 2017

Background/Aims: Perfusion magnetic resonance imaging (MRI) is useful for preoperative assessment of brain tumors. Dynamic susceptibility contrast perfusion MRI is commonly used for evaluation of brain tumors. Dynamic contrast-enhanced (DCE) MRI is an alternative method that has mainly been used in adult brain tumors. In this preliminary study, we report our initial experience with the DCE perfusion MRI in pediatric brain tumors. Methods: Sixty-four newly diagnosed pediatric brain tumor patients underwent DCE perfusion MRI on a 3-T scanner. Hemodynamic and kinetic parametric maps were generated and the regions with the highest values were measured on each map. Statistical differences were sought to differentiate between low-grade tumors, high-grade tumors, and medulloblastomas. The perfusion metrics of common posterior fossa tumors were also compared. Results: Relative corrected cerebral blood volume (rCBV) and fractional plasma volume measures differed significantly between high- and low-grade tumors (p < 0.05). High-grade tumors could be differentiated from low-grade tumors, with an rCBV cutoff value of 2.41 and 88.6% sensitivity and 65% specificity. There was no significant difference in Ktrans, Kep, Ve, or λtr between these 2 groups of tumors. rCBV, relative quantification of the cerebral blood flow, and permeability indices were found to be significantly different in various posterior fossa tumors, i.e., pilocytic astrocytoma, ependymoma, and medulloblastoma (p < 0.05). Conclusion: DCE-derived perfusion metrics are useful in differentiating high-grade tumors from low-grade ones and discriminating among various posterior fossa tumors in the pediatric age group.
Transformation of Cells by Photoinactivated Murine Gamma-Herpesvirus 68 during Nonproductive and Quiescent Infection
Authors: Mrázová Veronika , Kúdelová Marcela , Smolinská Miroslava , Nováková Eva , Šupolíková Miroslava , Vrbová Michaela , Golais František
Published: August 2017

Infection of human MRC-5 cells and mouse NIH-3T3 cells with a murine gamma-herpesvirus (MuHV-4 strain 68; MHV-68) photoinactivated by visible light in the presence of methylene blue (MB) resulted in nonproductive infection and the appearance of morphologically transformed cells. Two stably transformed cell lines were derived from both of these cell types and were confirmed to contain both viral DNA and antigen. Next, a quiescent MHV-68 infection in MRC-5 and NIH-3T3 cells was established after cultivation at 41°C in the presence of phosphonoacetic acid. Following the exposure of quiescently infected cells to visible light for 120 s (5 times daily for 6 days) in the presence of MB, both MRC-5 and NIH-3T3 cells were observed to acquire transformed phenotypes. The cytopathic effect was observed in cells after 4-5 passages, after which the cells degenerated. However, when human interferon (IFN)-α and mouse IFN-β were added to the media of quiescently infected MRC-5 and NIH-3T3 cells during the photoinactivating procedure, 2 stable transformed cell lines containing both viral DNA and the antigen were obtained and resembled those attained following nonproductive infection with photoinactivated virus.
Endoscopic Lung Volume Reduction: An Expert Panel Recommendation - Update 2017
Authors: Herth Felix J.F. , Slebos Dirk-Jan , Criner Gerard J. , Shah Pallav L.
Published: August 2017

Interest in endoscopic lung volume reduction (ELVR) technologies for emphysema is consistently growing. In the last couple of months, several endoscopic options (e.g., endo- or intrabronchial valves, coil implants, and thermal vapor ablation) that have been evaluated in randomized controlled trials have been reported with the ultimate goal of improving respiratory mechanics and alleviating chronic dyspnea. Patients presenting with severe air trapping and thoracic hyperinflation have the greatest potential to derive benefit from ELVR procedures. Baseline assessment should ideally include cardiological evaluation, high-resolution computed tomography scan and perfusion scintigraphy, full pulmonary function tests, and cardiopulmonary exercise testing. This expert statement updates best practice recommendations regarding patient selection and utilization of these various techniques for the treatment of patients with advanced emphysema.
Number of Oocytes Retrieved as a Criterion for “Freeze-All” Strategy versus a Single “Rescue” Bolus of Low-Dose Human Chorionic Gonadotropin Following GnRH Agonist for Ovulation Triggering: A Pilot Study
Authors: Rahav Koren Roni , Gonen Ofer , Hershko Klement Anat , Haikin Herzberger Einat , Ghetler Yehudith , Shulman Adrian , Wiser Amir
Published: August 2017

Aim: To evaluate the number of oocytes retrieved as a criterion - when to use a “freeze-all” or low-dose “rescue human chorionic gonadotropin (hCG)” strategy. Methods: A retrospective study. Instead of the classic hCG trigger, an E2 level of ≥3,000 pg/mL was used to trigger ovulation with GnRH agonist. The decision whether to “freeze all” or perform fresh embryo transfer (ET) with a bolus of hCG was made based on a maximum number of 20 oocytes retrieved. Beyond this cut off, a “freeze-all” strategy was implemented. Below this cut-off value, a fresh ET using a single bolus of 62.5 µg hCG on day 3 following oocyte pick-up was performed. The main outcome measures were clinical pregnancy rates and ovarian hyperstimulation syndrome (OHSS). Results: E2 and progesterone levels increased after the rescue hCG bolus administration (E2 from 643.4 ± 311.1 to 1,086.1 ± 574.7 pg/mL, p = 0.003 and progesterone from 13.1 ± 4.8 to 39.2 ± 28.7 ng/mL, p < 0.0001). The clinical pregnancy rates were 25% in the freeze-all group and 32% in the rescue hCG group (p = 0.57). OHSS was not reported in either group. Conclusions: Both strategies seem to be efficacious and safe. An upper limit of 20 retrieved oocytes appears to be safe for applying a rescue hCG strategy.
Effects of Inadequate Amino Acid Mixture Intake on Nutrient Supply of Adult Patients with Phenylketonuria
Authors: Hochuli Michel , Bollhalder Sandra , Thierer Carina , Refardt Julie , Gerber Philipp , Baumgartner Matthias R.
Published: August 2017

Background: Adult phenylketonuria (PKU) patients often reduce their intake of amino acid mixture (AAM) to less than the prescribed amounts. Effects of reduced AAM intake on nutrient supply were evaluated. Methods: Nutrient intake was calculated in 20 adult PKU patients based on a structured food record and complemented by laboratory assessment of nutritional status. Patients were classified into 2 groups, (A) regular AAM intake, or (B) AAM intake below calculated requirements. Results: Group B consumed a higher proportion of natural protein (60 ± 23 vs. 33 ± 12%, p = 0.002); however, the total protein intake was below the recommended amounts in 60% of patients in group B versus 7% in group A (p = 0.03). Fat intake was higher in group B (39 ± 9% of energy vs. 31 ± 6%, p = 0.03), mainly from saturated fats. Selenium, folate, and vitamin B12 intake was below the recommended intake in group B. However, serum concentrations of these analytes remained within the normal range in both groups, although vitamin B12 levels were lower in group B. Plasma tyrosine correlated with AAM intake, and hydroxyproline correlated with the amount of natural protein consumed. Conclusion: Relaxed AAM intake resulted in insufficient nutrient supply, despite a compensatory increase in consumption of natural protein. Care needs to be taken to ensure adequate nutrition in adults with PKU.
Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits
Authors: Svarstad Einar , Leh Sabine , Skrunes Rannveig , Kampevold Larsen Kristin , Eikrem Øystein , Tøndel Camilla
Published: August 2017

Background/Aims: A previous case report found stereomicroscopic changes typical for Fabry disease in a kidney biopsy. This case series evaluates an expanded diagnostic capacity of the method. Methods: Bedside stereomicroscopy was performed in a cross-sectional prospective study of 31 consecutive enzyme-treated or treatment-naïve male (n = 14) and female Fabry disease patients. The burden of glomerular storage material was scored semiquantitatively on a visual analog scale (range 0-3) and a blinded comparison was done with a reference histologic method. Results: Significant correlations (p < 0.001) were found between the stereomicroscopic scoring of glomerular characteristic white storage material and the amount of podocyte globotriaosylceramide (Gb3) deposits scored by standardized light microscopy. The bedside method correctly identified the variability of podocyte Gb3 accumulation after 10 years of identical agalsidase therapy in 2 brothers aged 24 and 27 years, and also identified tubular cell deposits. Stereomicroscopy correctly verified the absence of sphingolipid deposits in the biopsy of a female index patient with a genetic variant of unknown significance, and the diagnosis of Fabry disease was finally discarded. Conclusions: Bedside stereomicroscopy of kidney biopsies is an easily available, low-cost microscopy method handled by the clinician. The method carries a high diagnostic sensitivity for Fabry disease, reducing the risk of misdiagnosis in previously unknown cases. An expanded yield of the method is suggested, including the grading of the podocyte Gb3 burden and assessment of effectiveness of enzyme replacement therapy. We recommend the method as complementary to current standard histologic evaluation of Fabry kidney biopsies.
Pharmaceutical Perspective: How Digital Biomarkers and Contextual Data Will Enable Therapeutic Environments
Authors: Rodarte Carlos
Published: August 2017

Digital biomarkers are helping to reshape the understanding of health and disease, which will have an impact in how an individual’s relationship to the environment is assessed, how research is conducted, and how treatment effectiveness is determined. In particular, this article highlights key activities by the pharmaceutical industry as they explore the utility and relevance of digital biomarkers across the value chain. Lastly, this paper will discuss how digital biomarkers, in conjunction with digital environmental markers, will pave the way for the creation of healthy spaces that more directly improve patient outcomes.
VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway
Authors: Guo Jia , Lu Congqun , Zhang Fangxing , Yu Haixia , Zhou Mengwen , He Meixia , Wang Chunyan , Zhao Zhanzheng , Liu Zhangsuo
Published: August 2017

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease and proteinuria is one of the most prominent clinical manifestations. The expression of Vitamin D receptor (VDR) in patients with chronic kidney diseases was decreased, while VDR agonists could partially alleviate the proteinuria of DN in animal models. The present study was designed to determine the expression of VDR in renal tissues and its relationship with proteinuria the diabetic model db/db mice. Methods: The regulation effects of VDR on the Wnt signaling pathway were analyzed using RNA interference and VDR agonist paricalcitol. Results: With the increase in age of the db/db mice, the VDR protein and mRNA levels in renal tissues were decreased, proteinuria increased, and the protein and mRNA levels of GSK-3β of and β-catenin increased. Paricalcitol treatment resulted in the up-regulation of VDR and down-regulation of GSK-3β and β-catenin, indicating that VDR had a regulatory effect on the Wnt signaling pathway. Conclusion: VDR activation could reduce proteinuria of DN mice and alleviate high-glucose-induced injury of kidneys and podocytes by regulating the key molecules of Wnt signaling pathway.
Honokiol Attenuates Oligomeric Amyloid β1-42-Induced Alzheimer’s Disease in Mice Through Attenuating Mitochondrial Apoptosis and Inhibiting the Nuclear Factor Kappa-B Signaling Pathway
Authors: Wang Mo , Li Yu , Ni Changwei , Song Guijun
Published: August 2017

Background: Increasing evidence indicates that amyloid β oligomer (AβO) is toxic to neurons in Alzheimer’s disease (AD) brain. The aim of the present study is to evaluate the effects of honokiol on AβO-induced learning and memory dysfunction in mice. Methods: AD mice model was established by AβO intrahippocampal injection. The cognitive function was evaluated using Morris water maze (MWM). Nissl staining was used to examine the hippocampal neuron damage. Primary hippocampal neurons were exposed to AβO. The apoptosis in the hippocampal tissues and primary neurons was assessed using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling-neuronal nuclei (NeuN) and Hoechst staining, respectively. The mitochondrial membrane potential and radical oxygen species were detected using standard methods. Western blotting assay was used to check the expression levels of apoptotic and nuclear factor kappa-B (NF-κB) signaling-associated proteins and electrophoretic mobility shift assay was used to detect NF-κB-DNA binding. Results: Honokiol increased the time spend in the target zone of the AD mice in the MWM. In addition, honokiol dose-dependently attenuated AβO-induced hippocampal neuronal apoptosis, reactive oxygen species production and loss of mitochondrial membrane potential. Furthermore, AβO-induced NF-κB activation was inhibited by honokiol, as well as the upregulated amyloid precursor protein and β-secretase. Conclusion: Honokiol attenuates AβO-induced learning and memory dysfunction in mice and it may be a potential candidate in AD therapy.
Effect of the Diabetic Environment On the Expression of MiRNAs in Endothelial Cells: Mir-149-5p Restoration Ameliorates the High Glucose-Induced Expression of TNF-α and ER Stress Markers
Authors: Yuan Jing , Chen Minghao , Xu Qingyun , Liang Jianxin , Chen Ruixue , Xiao Ya , Fang Meixia , Chen Liguo
Published: August 2017

Background/Aims: This study aimed to screen microRNAs and their corresponding target genes that are associated with vascular injury in type two diabetes mellitus (T2DM), investigate the effects of differentially expressed miRNAs and their target genes on high glucose-induced vascular injury and establish the mechanism underlying these effects. Methods: A high-throughput digital gene expression (DGE) sequencing was performed to sequence microRNAs (miRNAs) and messenger RNAs (mRNAs) and determine their differential expression in human umbilical vein endothelial cells (HUVECs) incubated with serum samples from patients with T2DM and healthy volunteers. The HUVECs were transfected with si-TNF-α (tumor necrosis factor α) and a miR-149-5p inhibitor or mimic in vitro and then treated with normal or high glucose. The relative content of nitric oxide (NO) in the cells was detected using the Griess Reagent System. The mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were determined by qRT-PCR and Western blotting. The content of endothelin-1 (ET-1), von Willebrand factor (vWF), and intercellular adhesion molecular-1 (ICAM-1) were detected using an enzyme-linked immunosorbent assay (ELISA) kit. Apoptosis was determined by flow cytometry using the Annexin V/PI apoptosis detection kit. The mRNA and protein expression levels of ER stress (ERS) markers were determined by qRT-PCR and Western blotting. Results: Based on the high-energy sequencing and in vitro pre-experiment studies, we determined that miR-149-5p and TNF-α were a differentially expressed mRNA/miRNA pair in T2DM with vascular injury. The luciferase reporter assay results demonstrated that miR-149-5p could directly target TNF-α. The upregulation of miR-149-5p reduced the high glucose-induced dysfunction in the HUVECs by significantly decreasing the levels of ET-1, vWF, and ICAM-1 and increasing the level of NO and the expression of eNOS. Additionally, we found that miR-149-5p can improve cell injury and reduce apoptosis by restoring the ameliorated high glucose-induced expression of ERS markers. Conclusion: TNF-α and miR-149-5p were differentially expressed in T2DM vascular endothelial injury. The over-expression of miR-149-5p ameliorates the high glucose-induced injury in the HUVECs by regulating the expression of TNF-α and ERS markers.
Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors
Authors: Zhao Jiuda , Zhao Hong , Chi Yihebali
Published: August 2017

Purpose: Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods: A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m2 orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival. Results: Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively. Conclusions: The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.
Cardiovascular Magnetic Resonance to Predict Appropriate Implantable Cardioverter Defibrillator Therapy in Ischemic and Nonischemic Cardiomyopathy Patients Using Late Gadolinium Enhancement Border Zone
Authors: Jablonowski Robert , Chaudhry Uzma , van der Pals Jesper , Engblom Henrik , Arheden Håkan , Heiberg Einar , Wu Katherine C. , Borgquist Rasmus , Carlsson Marcus
Published: August 2017

Background—

Late gadolinium enhancement (LGE) border zone on cardiac magnetic resonance imaging has been proposed as an independent predictor of ventricular arrhythmias. The purpose was to determine whether size and heterogeneity of LGE predict appropriate implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients and to evaluate 4 LGE border-zone algorithms.

Methods and Results—

ICM and NICM patients who underwent LGE cardiac magnetic resonance imaging prior to ICD implantation were retrospectively included. Two semiautomatic algorithms, expectation maximization, weighted intensity, a priori information and a weighted border zone algorithm, were compared with a modified full-width half-maximum and a 2-3SD threshold-based algorithm (2-3SD). Hazard ratios were calculated per 1% increase in LGE. A total of 74 ICM and 34 NICM were followed for 63 months (1–140) and 52 months (0–133), respectively. ICM patients had 27 appropriate ICD events, and NICM patients had 7 ICD events. In ICM patients with primary prophylactic ICD, LGE border zone predicted ICD therapy in univariable and multivariable analysis measured by the expectation maximization, weighted intensity, a priori information, weighted border zone, and modified full-width half-maximum algorithms (hazard ratios 1.23, 1.22, and 1.05, respectively;
P
<0.05; negative predictive value 92%). For NICM, total LGE by all 4 methods was the strongest predictor (hazard ratios, 1.03–1.04;
P
<0.05), though the number of events was small.

Conclusions—

Appropriate ICD therapy can be predicted in ICM patients with primary prevention ICD by quantifying the LGE border zone. In NICM patients, total LGE but not LGE border zone had predictive value for ICD therapy. However, the algorithms used affects the predictive value of these measures.
(If) You Make Your Own Story
Authors: Kaler Ian
Published: August 2017

(If) You Make Your Own Story is a collage created from the series o.T. (Incipient Futures). o.T. is a study of the future through embodiment, alliance, and community.
“We Rule the Waves”: Athletic Labor, Femininity, and the Collective in Billy Rose’s Aquacade
Authors: Jahanmir Yasmine Marie
Published: August 2017

In the 1930s and ‘40s, nightclub impresario Billy Rose cast Olympic swimmers and divers in starring roles for his patriotic World’s Fair revue. Positioning the Aquacade in the genealogies of mass spectacles, militaristic display, girly revues, and the rising popularity of pool culture reveals the theatrical framing of athletic labor as vigorously effective in creating a visible female collective on the eve of World War II.
Lysander and the Execution of the Athenian Prisoners at Aegospotami (Xenophon, Hell. 2.1.31-32)
Authors: Kapellos Aggelos
Published: August 2017

Xenophon’s account allows us to suspect that Lysander killed the Athenian prisoners in the Hellespont because most of them were thetes, who he feared would make Athens strong again if they lived. The historian was unwilling for ideological reasons to say explicitly that the seamen of Athens were the real opponents of the Spartan commander on this occasion, but he expected that through his evasive writing his readers would conceive his message about Lysander.
Flora of Bokor National Park, Cambodia VI: A new species of Wikstroemia (Thymelaeaceae), W. bokorensis
Authors: OGURI EMIKO , TAGANE SHUICHIRO , CHHANG PHOURIN , TOYAMA HIRONORI , MURAKAMI NORIAKI , YAHARA TETSUKAZU
Published: August 2017

A new species, Wikstroemia bokorensis (Thymelaeaceae), from Bokor National Park, Kampot Province, Cambodia, is described and illustrated. This species is morphologically most similar to W. nutans distributed in southern China and Vietnam, but differs in having pubescent branches and leaves, smaller anthers, a single disk scale, and glabrous ovary. DNA barcodes of ITS, rbcL, trnT-F, rps16, and rpl16 regions for the new species are also provided.
Salacia fugax, an elusive new South American Salacioideae (Celastraceae)
Authors: LOMBARDI JULIO ANTONIO , SERNA GONZÁLEZ MARCELA
Published: August 2017

A new South American species of Salacia (Celastraceae, Salacioideae) found in Colombia and Venezuela, Salacia fugax Lombardi & M.Serna is described here. It is characterized by its indument, small long acuminate leaves with short petioles, branched inflorescences, flowers with an annular-pulvinate disk, and small pyriform fruits. This new species resembles S. mennegana J.Hedin ex Lombardi and S. opacifolia (J.F.Macbr.) A.C.Sm. by its short petioles, leaf shape, slender branched inflorescence, perianth form, and similar disc, but S. fugax differs by its hairs, leaf size and apex, calyx, and fruit size and shape.
Disentangling Astraea lobata: three new names in Astraea based on previous varieties of Croton lobatus (Euphorbiaceae)
Authors: SILVA OTÁVIO LUIS MARQUES DA , CORDEIRO INÊS
Published: August 2017

Within Astraea Klotzsch (1841: 194), Astraea lobata (Linnaeus 1753: 1005) Klotzsch (1841: 194) may be considered the most taxonomically complex species due to its wide geographical distribution and the several varieties that have been proposed for this species by Müller Argoviensis (1866, 1874). In his concept, Müller Argoviensis (1866) united under Croton lobatus Linnaeus (1753: 1005) plants with 3–5-partite leaves almost as long as the petioles, subulate stipules, the bracts not well developed and ovaries with varied indumentum. In De Candolles’s Prodromus, Müller Argoviensis (1866) recognized eight varieties, maintaining this concept in the Flora Brasiliensis (Müller Argoviensis 1874) with few modifications. Morphological characters and geographical distribution support the recognition of some of these varieties as species distinct from A. lobata. As part of an undergoing taxonomic revision of Astraea, these distinct taxa must be validly published for further studies on this genus. Therefore, in this note we propose these novelties with commentaries about morphology and geographic distribution, along with photos to illustrate them and lectotypifications when necessary.
New circumscription of Cryptanthus and new Cryptanthoid genera and subgenera (Bromeliaceae: Bromelioideae) based on neglected morphological traits and molecular phylogeny
Authors: LEME ELTON M. C. , HELLER SASCHA , ZIZKA GEORG , HALBRITTER HEIDEMARIE
Published: August 2017

The authors provide a new circumscription for genera of the “Cryptanthoid complex” of Bromeliaceae subfam. Bromelioideae, originally composed of Cryptanthus, Lapanthus, Orthophytum, and Sincoraea, on the basis of new or re-evaluated ecological, geographical and morphological evidence, as well as molecular phylogenies. A new generic status is proposed for Cryptanthus subg. Hoplocryptanthus and two new genera, Forzzaea, and Rokautskyia, as well as four new subgenera in Orthophytum (Capixabanthus, Clavanthus, Krenakanthus, and Orthocryptanthus) are described to render taxonomic units monophyletic. The recognized taxa are well circumscribed by the combination of geographical range, ecology and morphological characters (sex distribution, leaf succulence, sepal and petal size and connation, petal appendages, pollen and stigma morphology, fruit size, calyx persistency, seed size and number per fruit). Field collected living specimens of 78 of the 81 species of Cryptanthus s.l., all species of Lapanthus, 58 of the 59 species of Orthophytum, and all species of Sincoraea were analysed in habitat and/or in cultivation, allowing the documentation and illustration of new and underutilized characters. The molecular analysis incorporated 91 accessions representing 33 species of Cryptanthus, all species (3) of Lapanthus, 42 species of Orthophytum, and 9 species of Sincoraea, including the type species for the first three genera and four outgroup taxa. The results suggest, that some morphological characters generally considered homoplasious for Bromelioideae, for the “Cryptanthoid complex”, are not homoplasious at least within the obtained, biogeographycally well delimited clades and their taxonomical utility is redeemed.
Review of the Neotropical spider wasp subgenus Anoplius (Dicranoplius) Haupt (Hymenoptera: Pompilidae), new comb.
Authors: PITTS JAMES P. , WAICHERT CECILIA , SADLER EMILY
Published: August 2017

The genus Dicranoplius Haupt is reviewed and is treated as a subgenus of Anoplius, new comb., based on morphological and molecular evidence. This subgenus contains Anoplius albidus (Evans), A. areatus (Taschenberg), A. brevitarsus (Banks), A. cujanus (Holmberg), A. diphonichus (Spinola), A. nigritus (Evans), A. pampero (Evans), A. satanus (Holmberg), and A. evansi, sp. nov., newly described here from Colombia. Dicranoplius stangei Evans is considered a junior synonym of A. areatus (Taschenberg).
Hypokalaemia periodic paralysis
Authors: Stapleton Liam J
Published: August 2017

Hypokalaemic periodic paralysis is a rare skeletal muscle channelopathy causing flaccid paralysis, which predominantly presents in adolescents and young adults. I report a case of a 33-year-old Caucasian man who presented with sudden onset paralysis, following previous similar presentations without investigation. Blood tests revealed undetectable serum potassium levels in the context of paralysis. Other causes of hypokalaemia were excluded, and the patient was treated with planned lifelong prophylactic potassium replacement for a diagnosis of primary hypokalaemic periodic paralysis. This case demonstrates that, although rare, hypokalaemic periodic paralysis should be considered as a differential diagnosis in young patients who present with sudden flaccid paralysis and can easily be excluded by checking serum potassium levels at presentation.
Unipolarity’s unpeacefulness and US foreign policy: consequences of a ‘coherent system of irrationality’
Authors: Karkour Haro L
Published: August 2017

Drawing on Hans J. Morgenthau, this article argues that a key contributor to the unpeacefulness of the post–Cold War unipolar order was the irrationality of US foreign policy. Post–Cold War US foreign policy was irrational in that it failed to base its strategy on the prudent evaluation of the empirical facts in the social and political context in which it was formulated. Instead, it reinterpreted reality in terms of a simplistic picture of the world as accepted by US policymakers a priori, and sought the use of military force as the sole national security strategy to impose the inviolability of the ideals entailed in this picture. This turned post–Cold War US foreign policy into a self-contradictory endeavour as far as the results were concerned: not only did it confuse desirable for essential interests in standardising the enemy – whether Milosevic, Saddam or Qaddafi – to fit the a priori categorisation, but it also opened a gap between the desirable and the possible. For one thing such an irrational post–Cold War US foreign policy failed to accommodate or annul was the empirical reality of conflicting interests in the social and political contexts upon which it sought to impose its a priori picture. This resulted in consequences that were untenable from the standpoint of US objectives and international peace and security, contributing, overall, to the unpeacefulness of the post–Cold War unipolar order.
Digital images and globalized conflict
Authors: Blaagaard Bolette , Mortensen Mette , Neumayer Christina
Published: August 2017

As the number of digital images of globalized conflicts online grow, critical examination of their impact and consequence is timely. This editorial provides an overview of digital images and globalized conflict as a field of study by discussing regimes of visibility and invisibility, proximity and distance, and the multiplicity of images. It engages critically with these interlinking themes as they are addressed in the contributing articles to the Special Issue as well as beyond, asking how genres and tropes are reproduced, how power plays a role in access to images, and how the sheer quantity of conflict-related images raise issues of knowledge production and research.
No deal
Authors: Hawley Marlin F
Published: August 2017

The impact of the New Deal has been a topic of ongoing historical investigation, with, in the past few decades, substantive research in New Deal relief programs on Americanist archaeology by disciplinary historians. The application of resources newly available through relief programs varied considerably geographically however, and this article uses Kansas as a case study of a state in which there was no federal New Deal archaeology. The article explores archaeological research conducted in the state during this era by the Smithsonian Institution as well as an attempt to secure funding for systematic investigations by the University of Kansas. The article highlights several factors that forestalled use of relief funding for archaeology.
Delayed diagnosis of bronchial transection following blunt chest trauma
Authors: Mohammadzadeh Ali Reza , Kayalha Hamid
Published: August 2017

Diagnosis of blunt tracheobronchial injuries can be challenging. These injuries may appear within months or years following the initial trauma. In general, diagnosis and treatment of delayed presentation of tracheobronchial injuries are uncommon. Herein, we present the case of a 48-year-old woman with complete transection of the right bronchus that was diagnosed 50 days after the initial trauma. Reconstructive surgery of the bronchus was performed successfully without any need for pulmonary resection.
Is lack of breakfast contributing to nutrient deficits and poor nutritional indicators among adolescent girls?
Authors: Jeyakumar Angeline , Ghugre Padmini
Published: August 2017

Background:

Breakfast is considered the first and most important meal of the day. Missing the first meal may result in significant nutritional deficits, if not compensated in subsequent meals.

Aim:

To describe the nutrient intake through breakfast and to study its association with nutritional indicators among adolescent girls.

Methods:

A cross-sectional study among adolescent girls ( n = 565) 16–18 years was carried out in urban slums of Pune, Maharashtra, India. Haemoglobin was assessed by cyanmethemoglobin method. Nutritional status was assessed through anthropometry and three 24-hours diet recall. Z scores, independent sample test, and linear logistic regression were used to assess undernutrition, to compare means of nutrient intake and to associate nutrient intake with nutritional status, respectively.

Results:

Almost 50% did not consume solid food for breakfast and 99% of the participants consumed inadequate breakfast (<610 kcal). Two types of breakfast emerged: I (bakery products + beverage) and II (traditional breakfast + beverage). Although the mean energy intake of type II breakfast (235±100.55 kcal) and the mean micronutrient intake was significantly higher than type I (micronutrients: vitamin C and folate ( p = 0.001), iron ( p = 0.01)) it did not meet the adequacy norms for breakfast. Among nutritional indicators breakfast intake was not directly associated with body mass index. However, mean intake of nutrients such as energy, protein and iron through the day were significantly lesser ( p = 0.001, p = 0.01 and p = 0.01 respectively) among anaemic adolescents. Linear regression showed significant association between energy, fat intake and BAZ scores.

Conclusions:

Compensating dietary deficits that arise in the first meal would directly address the day’s nutrient deficit. The results highlight the need for a food-based approach to address undernutrition among adolescent girls in resource-poor settings.
The whale multiple: Spatial formations of whale tourism in Jangsaengpo, South Korea
Authors: Choi Myung-Ae
Published: August 2017

Whale-watching tourism is widely regarded as a manifestation of the transition from whale hunting to whale protection. However, in Jangsaengpo, South Korea, watching whales and eating whale-meat occur side by side for tourism purposes. Here, the concurrence of the two seemingly conflicting practices is legitimated through the by-catch which enables eating without killing by using “accidentally” caught whales for meat. Bringing together ontological discussions of multinaturalism and the topological analysis of space, this paper examines the ways in which spatial relations are performed to produce multiple whale ontologies within Jangsaengpo's whale tourism. It specifically unfolds diverse geographical connections (from Japan to the US), and their interactions, which enact whales in Jangsaengpo as a multiplicity – what I call “the whale multiple”. This paper first traces Jangsaengpo's historical and contemporary whale-related geographical connections through which an array of actors and entities are enrolled into, and transformed, within the assemblage of whale tourism. It then considers the spatial politics exercised through the by-catch, which configures a concurrence of conflicting whale ontologies. The paper discusses the political implications of the whale multiple which suggests strategic living with different ontological worlds as a way of moving beyond the killing–protecting antagonism. By illustrating the spatial production and configuration of ontological multiplicity, this paper engages with the spatial dimension of the multinatural theorisation of nature.