bluuebunny/crossref_metadata_2025 huggingface dataset:
Ureteral Dilatation with No Apparent Cause on Intravenous Urography: Normal or Abnormal? A Pilot Study
Authors: Rathi Vinita , Agrawal Sachin , Bhatt Shuchi , Sharma Naveen
Published: October 2015

A pilot study was done in 18 adults to assess the significance of ureteral dilatation having no apparent cause seen on Intravenous Urography (IVU). A clinicoradiological evaluation was undertaken to evaluate the cause of ureteral dilatation, including laboratory investigations and sonography of the genitourinary tract. This was followed, if required, by CT Urography (using a modified technique). In 9 out of 18 cases, the cause of ureteral dilatation on laboratory investigations was urinary tract infection (6) and tuberculosis (3). In the remaining 9 cases, CTU identified the cause as extrinsic compression by a vessel (3), extrinsic vascular compression of the ureter along with ureteritis (2), extrinsic vascular impression on the right ureter and ureteritis in the left ureter (1), ureteral stricture (2), and ureteral calculus (1). Extrinsic vascular compression and strictures did not appear to be clinically significant in our study. Hence, ureteral dilatation without any apparent cause on intravenous urogram was found to be clinically significant in 12 out of 18 (66.6%) cases. We conclude that ureteral dilatation with no apparent cause on IVU may indicate urinary tract tuberculosis, urinary tract infection (E. coli), or a missed calculus. Thus, cases with a dilated ureter on IVU, having no obvious cause, should undergo a detailed clinicoradiological evaluation and CTU should be used judiciously.
Research on Evaluation on Agility of Agile Supply Chain Network Based on Complex Network Theory
Authors: Xu Nai-Ru , Liu Jia-Bao
Published: October 2015

The paper tries to add the network structure factors of agile supply chain network into agility evaluation. The paper firstly presents three concepts including node strength centrality, betweenness centrality, and network centrality. They are used to calculate the weight of node enterprises in the agile supply chain network. And then, a series of agility indicators are designed to evaluate agility of agile supply chain network. AHP is used to calculate the weight of the indicators. Next, these indicators are used to get initial agility evaluation matrix by means of Delphi method, Data Mining, and so forth. Then FCE is used to calculate the membership degree on agility of node enterprises by combining the evaluation matrix with the weight of indicators. Last, the evaluation result of comprehensive agility of agile supply chain network is calculated on the basis of considering the weight of node enterprises. This method can reflect the effect which the network structure of supply chain network makes on the agility of the supply chain network. It is a complement to the current evaluation methods of agility.
Effects of Low-Dose Pioglitazone on Serum Levels of Adiponectin, Dehydroepiandrosterone, Amyloid Beta Peptide, and Lipid Profile in Elderly Japanese People with Type 2 Diabetes
Authors: Aoki Yuji
Published: October 2015

This study was performed to see how pioglitazone at low doses could affect blood biomarkers related to atherosclerosis and aging. The effects of an add-on treatment with pioglitazone (15 mg for males and 7.5 mg for females) for 6 months were assessed in 24 outpatients (12 males, 12 females) with type 2 diabetes aged ≥ 70 years. As doses of sulfonylurea were reduced in 10 patients, no significant differences in HbA1c and glucose levels were seen. After the treatment, serum levels of HDL cholesterol, arachidonic acid (predominant in males), and high-molecular-weight adiponectin significantly increased. The level of dehydroepiandrosterone sulfate significantly decreased. No significant changes were seen in those of small dense LDL cholesterol, high-sensitivity C-reactive protein, and amyloid beta peptides 1–40 and 1–42. There was a slight but significant increase in body weight, but apparent adverse effects were not observed. In conclusion, pioglitazone at low doses increased serum adiponectin, HDL cholesterol, and arachidonic acid levels but decreased serum dehydroepiandrosterone level, not associated with glycemia, in elderly Japanese people with type 2 diabetes. An optimal dose of pioglitazone should be sought for to minimize its adverse effects and to fully exert its pleiotropic effects such as antiatherosclerotic and antiaging effects.
Evaluation of Urban Infrastructure Investment Efficiency: Empirical Evidence from Heilongjiang Province, China
Authors: Yang Xiaodong , Wu Yongxiang , Yu Yafeng
Published: October 2015

The rapid growth of urban infrastructure investment in China has brought with it some serious problems that cannot be ignored, such as low investment efficiency and faulty investment decision-making. Therefore, based on the latest research findings related to infrastructure efficiency evaluation theory and evaluation methods, this paper uses empirical evidence from Heilongjiang province to analyze urban infrastructure investment efficiency. To analyze investment efficiency in the province, a new infrastructure investment efficiency evaluation model is developed known as the SDEA-Malmquist model. The model reveals that urban infrastructure investment projects in Heilongjiang province are relatively effective and stable but that the efficiency of such investments varies according to the city in which they are made. Overall efficiency is consistent with the TFC (total final consumption) index, but the index fluctuates within a narrow range between cities due to technological differences.
An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp
Authors: Jang Ji-Hyun , Shin Hee Woong , Lee Jung Min , Lee Hyeon-Woo , Kim Eun-Cheol , Park Sang Hyuk
Published: October 2015

Pathogen recognition receptors (PRRs) are a class of germ line‐encoded receptors that recognize pathogen‐associated molecular patterns (PAMPs). The activation of PRRs is crucial for the initiation of innate immunity, which plays a key role in first‐line defense until more specific adaptive immunity is developed. PRRs differ in the signaling cascades and host responses activated by their engagement and in their tissue distribution. Currently identified PRR families are the Toll‐like receptors (TLRs), the C‐type lectin receptors (CLRs), the nucleotide‐binding oligomerization domain‐like receptors (NLRs), the retinoic acid‐inducible gene‐I‐like receptors (RLRs), and the AIM2‐like receptor (ALR). The environment of the dental pulp is substantially different from that of other tissues of the body. Dental pulp resides in a low compliance root canal system that limits the expansion of pulpal tissues during inflammatory processes. An understanding of the PRRs in dental pulp is important for immunomodulation and hence for developing therapeutic targets in the field of endodontics. Here we comprehensively review recent finding on the PRRs and the mechanisms by which innate immunity is activated. We focus on the PRRs expressed on dental pulp and periapical tissues and their role in dental pulp inflammation.
Co-occurrence of Myeloproliferative Neoplasms and Solid Tumors Is Attributed to a Synergism Between Cytoreductive Therapy and the Common TERT Polymorphism rs2736100
Authors: Krahling Tunde , Balassa Katalin , Kiss Katalin Piroska , Bors Andras , Batai Arpad , Halm Gabriella , Egyed Miklos , Fekete Sandor , Remenyi Peter , Masszi Tamas , Tordai Attila , Andrikovics Hajnalka
Published: October 2015

Background: The germline telomerase reverse transcriptase (TERT) rs2736100_C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN).

Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100_C and Janus kinase 2 (JAK2) rs12343867_C tagging 46/1 haplotype in 584 BCR-ABL1–negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals.

Results: TERT rs2736100_C showed an increased allele frequency in BCR-ABL1–negative MPN patients compared with controls (62.7%±2.8% vs. 48.8%±3.5%, P < 0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4%) to die from solid tumors compared with TERT AC/AA individuals (5.3%; P = 0.004). TERT rs2736100_C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03–9.26), P = 0.045].

Conclusions: TERT rs2736100_C polymorphism predisposes to the development of BCR-ABL1–negative MPN with the co-occurrence of solid tumors, especially with the usage of cytoreductive treatment.

Impact: The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients. Cancer Epidemiol Biomarkers Prev; 25(1); 98–104. ©2015 AACR.
Lenvatinib in Advanced, Radioactive Iodine–Refractory, Differentiated Thyroid Carcinoma
Authors: Yeung Kay T. , Cohen Ezra E.W.
Published: October 2015

Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4–0.31; P < 0.0001). ORR was also significantly increased in the lenvatinib arm (64.7%) compared with placebo (1.5%). In this article, we will review the molecular mechanisms of lenvatinib, the data from preclinical studies to the recent phase III clinical trial, and the biomarkers being studied to further guide patient selection and predict treatment response. Clin Cancer Res; 21(24); 5420–6. ©2015 AACR.
Changes in T-Tubules and Sarcoplasmic Reticulum in Ventricular Myocytes in Early Cardiac Hypertrophy in a Pressure Overload Rat Model
Authors: Pérez-Treviño Perla , Pérez-Treviño Jorge , Borja-Villa Cuauhtémoc , García Noemí , Altamirano Julio
Published: October 2015

Background/Aims: Pressure-overload (PO) causes cardiac hypertrophy (CH), and eventually leads to heart failure (HF). HF ventricular myocytes present transverse-tubules (TT) loss or disarrangement and decreased sarcoplasmic reticulum (SR) density, and both contribute to altered Ca2+ signaling and heart dysfunction. It has been shown that TT remodeling precedes HF, however, it is unknown whether SR structural and functional remodeling also starts early in CH. Methods: Using confocal microscopy, we assessed TT (with Di-8-ANNEPS) and SR (with SR-trapped Mag-Fluo-4) densities, as well as SR fluorophore diffusion (fluorescence recovery after photobleach; FRAP), cytosolic Ca2+ signaling and ex vivo cardiac performance in a PO rat hypertrophy model induced by abdominal aortic constriction (at 6 weeks). Results: Rats developed CH, while cardiac performance, basal and upon β-adrenergic stimulation, remained unaltered. TT density decreased by ∼14%, without spatial disarrangement, while SR density decreased by ∼7%. More important, FRAP was ∼30% slower, but with similar maximum recovery, suggesting decreased SR interconnectivity. Systolic and diastolic Ca2+ signaling and SR Ca2+ content were unaltered. Conclusion: SR remodeling is an early CH event, similar to TT remodeling, appearing during compensated hypertrophy. Nevertheless, myocytes can withstand those moderate structural changes in SR and TT, preserving normal Ca2+ signaling and contractility.
sPLA2-IIA Augments Oxidized LDL-Induced MCP-1 Expression in Vitro Through Activation of Akt
Authors: Guo Yongjun , Li Bo , Xu Xuejing , Wu Rong , Li Weihua
Published: October 2015

Background/Aims: Group IIA secretory phospholipase A2 (sPLA2-IIA) has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. Methods: Human aortic smooth muscle cells (HASMCs) were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP). Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL), sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002. The mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) were assessed by quantitative real-time polymerase chain reaction (QRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Phosphorylation of Akt was examined by western blotting. Results: Lv-GFP-sPLA2-IIA-transduced HASMCs remained fluorescent during 72 h of the study period with infection ratio of around 80%. The mRNA expression and protein secretion of MCP-1was not altered in groups of HASMCs, Lv-GFP transduced and Lv-GFP-sPLA2-IIA-transduced HASMCs (p>0.05), but was significantly increased in the presence of oxidized LDL especially in Lv-GFP-sPLA2-IIA transduction group (p<0.01). However, with the addition of LY315920, this enhancement was notably decreased (p<0.05). This enhancement was also markedly abolished by co-incubation with LY294002, paralleled with suppressed Akt phosphorylation. Conclusions: Overexpression of sPLA2-IIA does not alter MCP-1 level at baseline, but could enhance the atherogenic effect of oxidized LDL in HASMCs, at least partly due to activation of Akt. These findings may provide a strategy for treatment of inflammatory cardiovascular diseases.
Dachengqi Decoction Attenuates Inflammatory Response via Inhibiting HMGB1 Mediated NF-κB and P38 MAPK Signaling Pathways in Severe Acute Pancreatitis
Authors: Chen Zhuoan , Chen Yafeng , Pan Liyun , Li Hongchang , Tu Jiamin , Liu Cheng , Dai Xiuqin , Zhang Xiaofen , Sun Guifang , Feng Dianxu
Published: October 2015

Background/Aims: Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest. Methods: In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD. Results: DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-kB and p38 MAPK pathway. Conclusion: Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure.
Long-Term Dietary Fructose Causes Gender-Different Metabolic and Vascular Dysfunction in Rats: Modulatory Effects of Resveratrol
Authors: Pektaş Mehmet Bilgehan , Sadi Gökhan , Akar Fatma
Published: October 2015

Background/Aims: There is limited knowledge on the gender differences in the effects of dietary fructose. In the current study, we investigated whether long-term fructose intake impacts metabolic parameters and vascular reactivity differently between male and female rats. Moreover, we tested whether resveratrol has a gender-specific effectiveness on the alterations. Methods: Male and female rats were divided into four groups as control; resveratrol; fructose and resveratrol plus fructose. Fructose was given to the rats as 10% solution in drinking water for 24 weeks. All rats were fed with the standard diet with or without resveratrol. Results: High-fructose diet increased plasma insulin, triglyceride and VLDL levels as well as omental weights in both genders. Long-term dietary fructose causes marked increase in body weight of males, but not females. Dietary fructose impaired endothelial relaxation to acetylcholine and intensified contraction to phenylephrine in the aortas of male and female rats, but differently it also reduced insulin-induced vasodilation in aortas of female rats. These changes were associated with decreased expression levels of endothelial nitric oxide synthase (eNOS) mRNA and protein, but increased in inducible NOS (iNOS), in aortas of male and female rats. Dietary fructose suppressed expression levels of sirtuin 1 (SIRT1) and insulin receptor substrate-2 (IRS-2) mRNA in aortas from female rats. Resveratrol supplementation efficiently restored fructose-induced metabolic and vascular dysfunction in both genders probably by regulating eNOS and iNOS production. Moreover, the augmentations in SIRT1 and IRS-2 mRNA in females and IRS-1 mRNA in males may possibly contribute to the beneficial effects of resveratrol as well. Conclusion: Long-term fructose intake may differently affect metabolic and vascular function between male and female rats, which are modified by resveratrol.
Advancing the Use of Clinical Decision Support to Prevent Drug-Associated AKI
Authors: Kane-Gill Sandra L. , Kellum John A.
Published: October 2015

Clinical decision support (CDS) has repeatedly been successful in improving the physicians' drug prescribing for patients with kidney disease. Alerts aimed at drug dosing may address prevention of drug accumulation, but might miss situations when a high-risk patient still receives a nephrotoxin. Alert advancement requires CDS that is focused on the appropriate use of potentially nephrotoxic medications. Unfortunately, the literature is replete with examples of inaccurate or ineffective alerts. However, analyzing these efforts will allow us to advance CDS to be more effective and to better understand how to include early detection of drug-associated acute kidney injury. Attempts have been made to address these limitations of CDS, but there are still opportunities for improvement.
Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2
Authors: Zhang Tao , Tian Feng , Wang Jing , Jing Jing , Zhou Shan-Shan , Chen Yun-Dai
Published: October 2015

Background/Aims: Endothelial cell injury and subsequent apoptosis play a key role in the development and pathogenesis of atherosclerosis, which is hallmarked by dysregulated lipid homeostasis, aberrant immunity and inflammation, and plaque-instability-associated coronary occlusion. Nevertheless, our understanding of the mechanisms underlying endothelial cell apoptosis is still limited. MicroRNA-429 (miR-29) is a known cancer suppressor that promotes cancer cell apoptosis. However, it is unknown whether miR-429 may be involved in the development of atherosclerosis through similar mechanisms. We addressed these questions in the current study. Methods: We examined the levels of endothelial cell apoptosis in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of anti-apoptotic protein Bcl-2 and the levels of miR-429 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-429 and 3'-UTR of Bcl-2 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-429 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. HFD mice had significantly lower percentage of endothelial cells and significantly higher percentage of mesenchymal cells in the aorta than NOR mice. Significantly higher levels of endothelial cell apoptosis were detected in HFD mice, resulting from decreases in Bcl-2 protein, but not mRNA. The decreases in Bcl-2 in endothelial cells were due to increased levels of miR-429, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Atherosclerosis-associated endothelial cell apoptosis may result from down regulation of Bcl-2, through increased miR-429 that binds and suppresses translation of Bcl-2 mRNA.
Is Hypothermia Helpful in Severe Subarachnoid Hemorrhage? An Exploratory Study on Macro Vascular Spasm, Delayed Cerebral Infarction and Functional Outcome after Prolonged Hypothermia
Authors: Kuramatsu Joji B. , Kollmar Rainer , Gerner Stefan T. , Madžar Dominik , Pisarčíková Andrea , Staykov Dimitre , Kloska Stephan P. , Doerfler Arnd , Eyüpoglu Ilker Y. , Schwab Stefan , Huttner Hagen B.
Published: October 2015

Background: Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated. Methods: This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome. Results: Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06). Conclusion: Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact.
Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring
Authors: Clemens Christoph R. , Eter Nicole
Published: October 2015

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.
Neuropsychological Evaluation and Cerebral Blood Flow Effects of Apolipoprotein E4 in Alzheimer's Disease Patients after One Year of Treatment: An Exploratory Study
Authors: Suwa Azusa , Nishida Keiichiro , Utsunomiya Keita , Nonen Shinpei , Yoshimura Masafumi , Takekita Yoshiteru , Wakeno Masataka , Tajika Aran , Yoshino Maki , Koshikawa Yosuke , Kato Masaki , Kinoshita Toshihiko
Published: October 2015

Background: Alzheimer's disease (AD) is affected by apolipoprotein E (ApoE); however, its effects assessed by means of cognitive tests and by neuroimaging have not been sufficiently studied. Methods: We administered the Alzheimer's Disease Assessment Scale (ADAS) and single-photon emission computed tomography imaging in patients with AD medicated with donepezil at baseline and after 1 year. Patients were classified as with or without ApoE4 and we evaluated the progress of AD. Results: Analysis of covariance showed that cerebral blood flow after 1 year in subjects with ApoE4 is significantly reduced in some areas including the left lenticular nucleus, left thalamus, and right hippocampus compared with subjects without ApoE4. Paired t tests showed significantly reduced blood flow in several regions including the right hippocampus in subjects with ApoE4 and significant deterioration of ideational praxis in subjects without ApoE4. Conclusion: This study provides evidence that supports the notion of ApoE4 playing an important role in the progress of AD.
Glycated Hemoglobin Value Combined with Initial Glucose Levels for Evaluating Mortality Risk in Patients with Ischemic Stroke
Authors: Roquer Jaume , Giralt-Steinhauer Eva , Cerdà Georgina , Rodríguez-Campello Ana , Cuadrado-Godia Elisa , Jiménez-Conde Jordi , Vivanco-Hidalgo Rosa Maria , Soriano Carol , Dégano Irene R. , Ois Angel
Published: October 2015

Background: Hyperglycemia is a marker of poor outcome in acute ischemic stroke (IS) patients. We aimed at evaluating the effect of combined HbA1c and first glucose measurement values on 3-month mortality prediction. Methods: In a prospective analysis, 1,317 first-ever IS patients with HbA1c values were classified by first glycemia value (<155, 155-199, ≥200 mg/dl). Three-month mortality was analyzed by glycemia category in nondiabetics, diabetics with good previous glucose control (PGC) (HbA1c <7%), and diabetics with poor PGC (HbA1c ≥7.0%). Results: Mortality at 3 months was 13.1%, with no differences (p = 0.339) between non-diabetes mellitus (DM) (12.3%), good PGC-DM (12.4%), and poor PGC-DM (15.6%) patients. The unadjusted relative risk of 3-month mortality for patients with glucose ≥200 mg/dl was 3.76 (95% CI 1.48-9.56) in non-DM, 6.10 (95% CI 1.76-21.09) in good PGC-DM, and 1.44 (95% CI 0.77-2.69) in poor PGC-DM. Glycemia cutoffs most highly correlated with mortality increased as PGC declined: 107 mg/dl in non-DM, 152 mg/dl in good PGC-DM, and 229 mg/dl in poor PGC-DM patients. Glycemia correlated with stroke severity in nondiabetics and diabetic patients with good PGC, but not in those with poor PGC. Conclusions: HbA1c determination combined with first measured glucose value is useful to stratify mortality risk in IS patients: hyperglycemia is a poor prognostic marker in non-DM and DM patients with good PGC; results are inconsistent in poor PGC-DM patients. Our data suggest the relationship between hyperglycemia and poor outcome reflects stress response rather than a deleterious effect of glucose.
‘Stroke Room': Diagnosis and Treatment at a Single Location for Rapid Intraarterial Stroke Treatment
Authors: Ragoschke-Schumm Andreas , Yilmaz Umut , Kostopoulos Panagiotis , Lesmeister Martin , Manitz Matthias , Walter Silke , Helwig Stefan , Schwindling Lenka , Fousse Mathias , Haass Anton , Garner Dominique , Körner Heiko , Roumia Safwan , Grunwald Iris , Nasreldein Ali , Halmer Ramona , Liu Yang , Schlechtriemen Thomas , Reith Wolfgang , Fassbender Klaus
Published: October 2015

Background: For patients with acute ischemic stroke, intra-arterial treatment (IAT) is considered to be an effective strategy for removing the obstructing clot. Because outcome crucially depends on time to treatment (‘time-is-brain' concept), we assessed the effects of an intervention based on performing all the time-sensitive diagnostic and therapeutic procedures at a single location on the delay before intra-arterial stroke treatment. Methods: Consecutive acute stroke patients with large vessel occlusion who obtained IAT were evaluated before and after implementation (April 26, 2010) of an intervention focused on performing all the diagnostic and therapeutic measures at a single site (‘stroke room'). Result: After implementation of the intervention, the median intervals between admission and first angiography series were significantly shorter for 174 intervention patients (102 min, interquartile range (IQR) 85-120 min) than for 81 control patients (117 min, IQR 89-150 min; p < 0.05), as were the intervals between admission and clot removal or end of angiography (152 min, IQR 123-185 min vs. 190 min, IQR 163-227 min; p < 0.001). However, no significant differences in clinical outcome were observed. Conclusion: This study shows for the, to our knowledge, first time that for patients with acute ischemic stroke, stroke diagnosis and treatment at a single location (‘stroke room') saves crucial time until IAT.
Reversible Growth Hormone Excess in Two Girls with Neurofibromatosis Type 1 and Optic Pathway Glioma
Authors: Bruzzi Patrizia , Sani Ilaria , Albanese Assunta
Published: October 2015

Background: A total of 12 children with neurofibromatosis type 1 (NF-1) with optic pathway glioma (OPG) and growth hormone (GH) excess are reported to date, but no data exist on the long-term outcome. We describe 2 girls with NF-1 with OPG and GH excess treated with somatostatin analogue (SSa) who maintained a normal GH axis after stopping SSa therapy. Methods: The diagnosis of GH excess was established from auxological data, persistently high levels of insulin-like growth factor 1 (IGF-1) and a lack of GH suppression during an oral glucose tolerance test. Results: Both patients were started on SSa treatment. During treatment, growth deceleration and normal IGF-1 levels were documented. The first case stopped treatment following the development of SSa side effects. The second case interrupted SSa when, closed to her final height, a normal IGF-1 level was documented. While off treatment, both cases maintained normal IGF-1 levels and appropriate growth velocity for their age and development, with normal GH secretion on biochemical testing. Both cases received treatment for central precocious puberty. Conclusion: GH excess in NF-1 children with OPG can be reversed and only short-term SSa therapy may be required. The aetiology remains undetermined, but the course suggests a hypothalamic dysfunction.
Measures to Assure that Ebola Guidelines Are Correctly Applied
Authors: Mira José Joaquín , Asencio-Aznar Alberto , Gea Teresa , Lorenzo Susana , Antón Pedro
Published: October 2015

Objective: The purpose of this study was to assure the application, in our primary care health district, of the World Health Organisation and Spanish Ebola virus disease (EVD) guidelines, and to identify and resolve gaps, in order to protect professionals from the risks associated with attending to patients with Ebola. Materials and Methods: A checklist was drawn up and an audit procedure of the structural, functional and operational conditions was designed for managing a self-presenting patient suspected with EVD in general practice. This audit was applied twice (before and after assessment) in 9 health centres of a health district in Spain. The checklist was structured according to 9 categories (51 elements in total). This tool was designed to avoid errors in the management of EVD patients that are considered very serious in view of their potential consequences. Results: Of the 51 elements on the checklist, 7-26 (14-51%) required direct intervention to rectify deficits in the first audit. The following elements requiring improvement were identified: the incorporation of memory aids to ensure the correct application of the EVD protocol, defining what information should be provided to the patient and (where applicable) anyone accompanying them as well as incorporating advice on how to deal with any individuals with whom they might have come into contact. A second audit assured the adequacy of the proposed solutions. Conclusion: In this study, the tool achieved the successful application of EVD protocol, assuring that primary care centres were able to handle an Ebola suspect patient safely.
Involvement of Membrane Blebbing in Immunological Disorders and Cancer
Authors: Khajah Maitham A. , Luqmani Yunus A.
Published: October 2015

Cellular blebbing is a unique form of dynamic protrusion emanating from the plasma membrane which can be either apoptotic or nonapoptotic in nature. Blebs have been observed in a wide variety of cell types and in response to multiple mechanical and chemical stimuli. They have been linked to various physiological and pathological processes including tumor motility and invasion, as well as to various immunological disorders. They can form and retract extremely rapidly in seconds or minutes, or slowly over hours or days. This review focuses on recent evidence regarding the role of blebbing in cell locomotion with particular emphasis on its role in tumor metastasis, indicating the role of specific causative molecules. The phenomenon of blebbing has been observed in endocrine-resistant breast cancer cells in response to brief exposure to extracellular alkaline pH, which leads to enhanced invasive capacity. Genetic or pharmacological targeting of cellular blebs could serve as a potential therapeutic option to control tumor metastasis.
Modest Associations Between Electronic Health Record Use and Acute Myocardial Infarction Quality of Care and Outcomes
Authors: Enriquez Jonathan R. , de Lemos James A. , Parikh Shailja V. , Simon DaJuanicia N. , Thomas Laine E. , Wang Tracy Y. , Chan Paul S. , Spertus John A. , Das Sandeep R.
Published: October 2015

Background—

In 2009, national legislation promoted wide-spread adoption of electronic health records (EHRs) across US hospitals; however, the association of EHR use with quality of care and outcomes after acute myocardial infarction (AMI) remains unclear.

Methods and Results—

Data on EHR use were collected from the American Hospital Association Annual Surveys (2007–2010) and data on AMI care and outcomes from the National Cardiovascular Data Registry Acute Coronary Treatment and Interventions Outcomes Network Registry-Get With The Guidelines. Comparisons were made between patients treated at hospitals with fully implemented EHR (n=43 527), partially implemented EHR (n=72 029), and no EHR (n=9270). Overall EHR use increased from 82.1% (183/223) hospitals in 2007 to 99.3% (275/277) hospitals in 2010. Patients treated at hospitals with fully implemented EHRs had fewer heparin overdosing errors (45.7% versus 72.8%;
P
<0.01) and a higher likelihood of guideline-recommended care (adjusted odds ratio, 1.40 [confidence interval, 1.07–1.84]) compared with patients treated at hospitals with no EHR. In non–ST-segment–elevation AMI, fully implemented EHR use was associated with lower risk of major bleeding (adjusted odds ratio, 0.78 [confidence interval, 0.67–0.91]) and mortality (adjusted odds ratio, 0.82 [confidence interval, 0.69–0.97]) compared with no EHR. In ST-segment–elevation MI, outcomes did not significantly differ by EHR status.

Conclusions—

EHR use has risen to high levels among hospitals in the National Cardiovascular Data Registry. EHR use was associated with less frequent heparin overdosing and modestly greater adherence to acute MI guideline-recommended therapies. In non–ST-segment–elevation MI, slightly lower adjusted risk of major bleeding and mortality were seen in hospitals implemented with full EHRs; however, in ST-segment–elevation MI, differences in outcomes were not seen.
Identifying Novel Gene Variants in Coronary Artery Disease and Shared Genes With Several Cardiovascular Risk Factors
Authors: LeBlanc Marissa , Zuber Verena , Andreassen Bettina Kulle , Witoelar Aree , Zeng Lingyao , Bettella Francesco , Wang Yunpeng , McEvoy Linda K. , Thompson Wesley K. , Schork Andrew J. , Reppe Sjur , Barrett-Connor Elizabeth , Ligthart Symen , Dehghan Abbas , Gautvik Kaare M. , Nelson Christopher P. , Schunkert Heribert , Samani Nilesh J. ,   CARDIoGRAM Consortium, Ridker Paul M , Chasman Daniel I. , Aukrust Pål , Djurovic Srdjan , Frigessi Arnoldo , Desikan Rahul S. , Dale Anders M. , Andreassen Ole A.
Published: October 2015

Rationale:

Coronary artery disease (CAD) is a critical determinant of morbidity and mortality. Previous studies have identified several cardiovascular disease risk factors, which may partly arise from a shared genetic basis with CAD, and thus be useful for discovery of CAD genes.

Objective:

We aimed to improve discovery of CAD genes and inform the pathogenic relationship between CAD and several cardiovascular disease risk factors using a shared polygenic signal–informed statistical framework.

Methods and Results:

Using genome-wide association studies summary statistics and shared polygenic pleiotropy-informed conditional and conjunctional false discovery rate methodology, we systematically investigated genetic overlap between CAD and 8 traits related to cardiovascular disease risk factors: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, C-reactive protein, body mass index, systolic blood pressure, and type 1 diabetes mellitus. We found significant enrichment of single-nucleotide polymorphisms associated with CAD as a function of their association with low-density lipoprotein, high-density lipoprotein, triglycerides, type 2 diabetes mellitus, C-reactive protein, body mass index, systolic blood pressure, and type 1 diabetes mellitus. Applying the conditional false discovery rate method to the enriched phenotypes, we identified 67 novel loci associated with CAD (overall conditional false discovery rate <0.01). Furthermore, we identified 53 loci with significant effects in both CAD and at least 1 of low-density lipoprotein, high-density lipoprotein, triglycerides, type 2 diabetes mellitus, C-reactive protein, systolic blood pressure, and type 1 diabetes mellitus.

Conclusions:

The observed polygenic overlap between CAD and cardiometabolic risk factors indicates a pathogenic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to CAD.
Cardiac Diseases Following Childhood Cancer Treatment
Authors: Haddy Nadia , Diallo Stéphanie , El-Fayech Chiraz , Schwartz Boris , Pein François , Hawkins Mike , Veres Cristina , Oberlin Odile , Guibout Catherine , Pacquement Hélène , Munzer Martine , N’Guyen Tan Dat , Bondiau Pierre-Yves , Berchery Delphine , Laprie Anne , Scarabin Pierre-Yves , Jouven Xavier , Bridier André , Koscielny Serge , Deutsch Eric , Diallo Ibrahima , de Vathaire Florent
Published: October 2015

Background—

Cardiac disease (CD) is one of the major side effects of childhood cancer therapy, but until now little has been known about the relationship between the heart radiation dose (HRD) received during childhood and the risk of CD.

Methods and Results—

The cohort comprised 3162 5-year survivors of childhood cancer. Chemotherapy information was collected and HRD was estimated. There were 347 CDs in 234 patients, 156 of them were rated grade ≥3. Cox and Poisson regression models were used. The cumulative incidence of any type of CD at 40 years of age was 11.0% (95% confidence interval [CI], 9.5–12.7) and 7·4% (95% CI, 6.2–8.9) when only the CDs of grade ≥3 were considered. In comparison with patients who received no anthracycline and either no radiotherapy or an HRD<0·1Gy, the risk was multiplied by 18·4 (95% CI, 7.1–48.0) in patients who had received anthracycline and no radiotherapy or a HRD <0.1Gy, by 60.4 (95% CI, 22.4–163.0) in those who had received no anthracycline and an HRD≥30Gy, and 61.5 (95% CI, 19.6–192.8) in those who had received both anthracycline and an HRD≥30Gy.

Conclusions—

Survivors of childhood cancers treated with radiotherapy and anthracycline run a high dose-dependent risk of developing CD. CDs develop earlier in patients treated with anthracycline than in those treated without it.
Constraining Elites: The Impact of Treaty Networks on Foreign Policy
Authors: Slobodchikoff Michael O.
Published: October 2015

In democracies, elites should be responsive to public opinion. This is especially true in Eastern Europe, where politicians fear electoral sanctions in the process of reform (Roberts and Kim 2011). Public opinion in general in Eastern Europe has been overwhelmingly in favor of European integration (Caplanova et al. 2004). In Ukraine, public opinion was in favor of increased cooperation with the eu, while in Moldova, public opinion was in favor of increased cooperation with the Russian led Customs Union. Ukraine refused to sign an association agreement with the eu, while Moldova enthusiastically signed the same association agreement. Why should both Ukrainian and Moldovan political elites have chosen not to be responsive to public opinion in such an important decision? Using network analysis of bilateral treaties between Russia and Moldova and Russia and Ukraine, I predict the responsiveness of political elites to public opinion toward European integration. I argue that the denser a treaty network between a weaker state and the regional hegemon, the less likely political elites will be to cooperate and move toward European integration. Conversely, less dense treaty networks allow politicians more flexibility in following their own preferences. Further, I offer a prediction for other states in the fsu to seek further cooperation with the eu.
Documenting Contested Racial Identities Among Self-Identified Latina/os, Asians, Blacks, and Whites
Authors: Vargas Nicholas , Stainback Kevin
Published: October 2015

A contested racial identity refers to incongruence between personal racial identification and external racial categorization. For example, an individual may self-identify as White, but be perceived by most others as non-White. Documenting racial contestation is important because racialized experiences are shaped not only by the racial classification that individuals claim for themselves but also the external racial attributions placed on them by others. Focusing solely on monoracial identifying adults, this study answers three key questions about racial contestation: (a) How common is it? (b) Who is most likely to report experiencing it? and (c) How is it related to aspects of racial identity such as racial awareness, racial group closeness, and racial identity salience? Employing the 2006 Portraits of American Life Study, results suggest that reports of racial contestation among monoracial identifying adults are more common than some studies suggest (6% to 14%)—particularly among the fastest growing racial groups in the United States, including Latina/os and Asians—and that experiences of racial contestation are often associated with immigrant generation, ancestry, and phenotypical characteristics. Ordinal logistic regression analyses indicate that individuals who report experiencing racial contestation are no more aware of race in everyday life than other U.S. adults, but they feel less close to other members of the self-identified racial group and report lower levels of racial identity salience than their noncontested counterparts. These results point to a thinning of racial identity among the racially contested.
Climate Change Deniers and Advocacy
Authors: Xifra Jordi
Published: October 2015

Climate change denial (i.e., organized attempts to downplay, deny, or dismiss scientific consensus on the extent of global warming, its significance, and its connection to human behavior) has been a recurrently researched topic in the United States, but is far less studied in Europe, where it is currently gathering force. The truth is that, as in the United States, climate deniers are a tiny minority in Europe. Their numbers contrast starkly with the overwhelming majority of scientists who agree on the reality of man-made climate change and the urgent need for action. However, the voices of climate deniers in Europe are amplified by a handful of influence groups, mainly think tanks, which consistently conceal their sources of funding and final interests. This situation can be approached from a strategic communication perspective, specifically within the framework of the situational theory of publics. From this standpoint, the knowledge of different variables relating to publics in a given situation regarding a public issue (like climate change) can determine the communication strategies chosen by deniers to amplify climate change denial arguments and will introduce their main communication strategies and messages.
For the Love of Death
Authors: Knafo Danielle
Published: October 2015

The psychoanalytic literature on somnophilic and necrophilic fantasies and acts is indeed sparse. It is argued here that one must distinguish the forms of fantasy, playacting, and actual behavior that lie along a spectrum of romantic or sexual behavior involving people who are sleeping, drugged, immobile, inanimate, comatose, or dead. Regardless of these distinctions, however, the underlying dynamics commonly involve reunion with the mother, an inability to mourn, fear of the female, and an attempt at mastering and transcending the fear of death. To highlight these psychodynamics, a clinical case of somnophilia, Pedro Almodóvar’s Talk to Her (a film about romantic relationships with comatose women), and the case of Count von Cosel, a quixotic necrophiliac, are presented. Gender differences are emphasized in the analysis of case material and cultural tropes.