bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Intolerance to Casting the Upper Extremities in Claustrophobic Patients
Authors: Nagura Issei , Kanatani Takako , Sumi Masatoshi , Inui Atsuyuki , Mifune Yutaka , Kokubu Takeshi , Kurosaka Masahiro
Published: October 2014

Introduction. Some patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities. We hypothesized their that intolerance with excessive anxiety to casts is due to claustrophobia triggered by cast immobilization. The aim of this study is to analyze the relevance of cast immobilization to the feeling of claustrophobia and discover how to handle them.Methods. There were nine patients who showed the caustrophobic symptoms with their casts. They were assesed whether they were aware of their claustrophobis themselves. Further we investigated the alternative immobilization to casts.Results. Seven out of nine cases that were aware of their claustrophobic tendencies either were given removable splints initially or had the casts converted to removable splints when they exhibited symptoms. The two patients who were unaware of their latent claustrophobic tendencies were identified when they showed similar claustrophobic symptoms to the previous patients soon after short arm cast application. We replaced the casts with removable splints. This resolved the issue in all cases.Conclusions. We should be aware of the claustrophobia if patients showed unusual responses to the immobilization without any objective findings with casts in upper extremities, where removal splint is practical alternative to cast to continue the treatment successfully.
General Split Variational Inclusion Problem in Hilbert Spaces
Authors: Yang Li , Zhao Fu Hai
Published: October 2014

We consider a general split variational inclusion problem (GSFVIP) and propose an algorithm for finding the solutions of GSFVIP in Hilbert space. We establish the strong convergence of the proposed algorithm to a solution of GSFVIP. Our results extend and improve the related results in the literature.
On the Exact Series Solution for Nonhomogeneous Strongly Coupled Mixed Parabolic Boundary Value Problems
Authors: Soler Vicente , Defez Emilio , Capilla Roberto , Verdoy José Antonio
Published: October 2014

An exact series solution for nonhomogeneous parabolic coupled systems of the typeut-Auxx=Gx, t, A1u0, t+B1ux0, t=0, A2ul, t+B2uxl, t=0, 0<x<1, t>0, ux, 0=fx, whereA1, A2, B1, andB2are arbitrary matrices for which the block matrix is nonsingular, andAis a positive stable matrix, is constructed.
miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model
Authors: Todorova Krassimira , Zasheva Diana , Kanev Kristiyan , Hayrabedyan Soren
Published: October 2014

Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660). We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.
Inductive and Deductive Approaches to Acute Cell Injury
Authors: DeGracia Donald J. , Tri Anggraini Fika , Taha Doaa Taha Metwally , Huang Zhi-Feng
Published: October 2014

Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems.
Efficient Recursive Methods for Partial Fraction Expansion of General Rational Functions
Authors: Ma Youneng , Yu Jinhua , Wang Yuanyuan
Published: October 2014

Partial fraction expansion (pfe) is a classic technique used in many fields of pure or applied mathematics. The paper focuses on the pfe of general rational functions in both factorized and expanded form. Novel, simple, and recursive formulas for the computation of residues and residual polynomial coefficients are derived. The proposed pfe methods require only simple pure-algebraic operations in the whole computation process. They do not involve derivatives when tackling proper functions and require no polynomial division when dealing with improper functions. The methods are efficient and very easy to apply for both computer and manual calculation. Various numerical experiments confirm that the proposed methods can achieve quite desirable accuracy even for pfe of rational functions with multiple high-order poles or some tricky ill-conditioned poles.
Molecular Population Structure ofJunoniaButterflies from French Guiana, Guadeloupe, and Martinique
Authors: Gemmell Amber P. , Borchers Tanja E. , Marcus Jeffrey M.
Published: October 2014

Up to 9 described species ofJunoniabutterflies occur in the Americas, but authorities disagree due to species similarities, geographical and seasonal variability, and possible hybridization. In dispute is whether CaribbeanJunoniaare conspecific with South American species.Cytochrome oxidase I(COI) barcodes,wingless(wg) sequences, and Randomly Amplified Fingerprints (RAF) were studied to revealJunoniapopulation structure in French Guiana, Guadeloupe, Martinique, and Argentina. Phylogenetic analysis ofCOIrecovered 2 haplotype groups, but mostJunoniaspecies can have either haplotype, soCOIbarcodes are ambiguous. Analysis of nuclearwinglessalleles revealed geographic patterns but did not identifyJunoniaspecies. Nuclear RAF genotyping distinguished 11 populations ofJunoniaarranged into 3 clusters. Gene flow occurs within clusters but is limited between clusters. One cluster included all Argentinian samples. Two clusters included samples from French Guiana, Martinique, and Guadeloupe and appear to be divided by larval host plant use (Lamiales versus Scrophulariales). ManyJunoniataxa were distributed across populations, possibly reflecting patterns of genetic exchange. We had difficulty distinguishing between the Caribbean formsJ. zonalisandJ. neildi, but we demonstrate that CaribbeanJunoniaare genetically distinct from South AmericanJ. evareteandJ. genoveva, supporting the taxonomic hypothesis that they are heterospecific.
Certain Families of Multivalent Analytic Functions Associated with Iterations of the Owa-Srivastava Fractional Differintegral Operator
Authors: Mishra A. K. , Kund S. N.
Published: October 2014

By making use of a multivalent analogue of the
Owa-Srivastava fractional differintegral operator and its
iterations, certain new families of analytic functions are
introduced. Several interesting properties of these function
classes, such as convolution theorems, inclusion theorems, and
class-preserving transforms, are studied.
Common Genetic Variants in NEFL Influence Gene Expression and Neuroblastoma Risk
Authors: Capasso Mario , Diskin Sharon , Cimmino Flora , Acierno Giovanni , Totaro Francesca , Petrosino Giuseppe , Pezone Lucia , Diamond Maura , McDaniel Lee , Hakonarson Hakon , Iolascon Achille , Devoto Marcella , Maris John M.
Published: October 2014

The genetic etiology of sporadic neuroblastoma is still largely obscure. In a genome-wide association study, we identified single-nucleotide polymorphisms (SNP) associated with neuroblastoma at the CASC15, BARD1, LMO1, DUSP12, HSD17B12, HACE1, and LIN28B gene loci, but these explain only a small fraction of neuroblastoma heritability. Other neuroblastoma susceptibility genes are likely hidden among signals discarded by the multiple testing corrections. In this study, we evaluated eight additional genes selected as candidates for further study based on proven involvement in neuroblastoma differentiation. SNPs at these candidate genes were tested for association with disease susceptibility in 2,101 cases and 4,202 controls, with the associations found replicated in an independent cohort of 459 cases and 809 controls. Replicated associations were further studied for cis-effect using gene expression, transient overexpression, silencing, and cellular differentiation assays. The neurofilament gene NEFL harbored three SNPs associated with neuroblastoma (rs11994014: Pcombined = 0.0050; OR, 0.88; rs2979704: Pcombined = 0.0072; OR, 0.87; rs1059111: Pcombined = 0.0049; OR, 0.86). The protective allele of rs1059111 correlated with increased NEFL expression. Biologic investigations showed that ectopic overexpression of NEFL inhibited cell growth specifically in neuroblastoma cells carrying the protective allele. NEFL overexpression also enhanced differentiation and impaired the proliferation and anchorage-independent growth of cells with protective allele and basal NEFL expression, while impairing invasiveness and proliferation of cells homozygous for the risk genotype. Clinically, high levels of NEFL expression in primary neuroblastoma specimens were associated with better overall survival (P = 0.03; HR, 0.68). Our results show that common variants of NEFL influence neuroblastoma susceptibility and they establish that NEFL expression influences disease initiation and progression. Cancer Res; 74(23); 6913–24. ©2014 AACR.
DUSP1 Phosphatase Regulates the Proinflammatory Milieu in Head and Neck Squamous Cell Carcinoma
Authors: Zhang Xiaoyi , Hyer J. Madison , Yu Hong , D'Silva Nisha J. , Kirkwood Keith L.
Published: October 2014

DUSP1 is a dual-specificity phosphatase that regulates mitogen-activated protein (MAP) kinase activity. Studies have associated loss of DUSP1 expression with certain cancers, but there has been no report of a mechanism by which this supports tumor progression. In this study, we found DUSP1 mRNA and protein decreased in human head and neck squamous cell carcinoma tissues compared with adjacent nontumor controls. To evaluate the impact of this difference, we compared the susceptibility of Dusp1-deficient mice with oral squamous carcinogenesis induced by 4-nitroquinoline 1-oxide. Dusp1-deficient mice displayed enhanced disease progression, characterized by advanced onset, histologic stage, and tumor burden. In a syngeneic model of tumor progression, subcutaneous injection of EO771 cells formed faster-growing tumors in Dusp1-deficient mice, an effect abrogated by inhibition of p38 MAP kinase with SB203580. Histologic and quantitative assessments demonstrated increased inflammation and deregulated chemokine and cytokine expression in Dusp1-deficient tumor tissues. Specifically, proinflammatory cytokine IL1β was elevated. IL1β production was recapitulated ex vivo in primary bone marrow–derived macrophages from Dusp1-deficient mice. Together, our results clearly establish the role of Dusp1 as a tumor suppressor gene that regulates cancer-associated inflammation. Cancer Res; 74(24); 7191–7. ©2014 AACR.
NT113, a Pan-ERBB Inhibitor with High Brain Penetrance, Inhibits the Growth of Glioblastoma Xenografts with EGFR Amplification
Authors: Yoshida Yasuyuki , Ozawa Tomoko , Yao Tsun-Wen , Shen Wang , Brown Dennis , Parsa Andrew T. , Raizer Jeffrey J. , Cheng Shi-Yuan , Stegh Alexander H. , Mazar Andrew P. , Giles Francis J. , Sarkaria Jann N. , Butowski Nicholas , Nicolaides Theodore , James C. David
Published: October 2014

This report describes results from our analysis of the activity and biodistribution of a novel pan-ERBB inhibitor, NT113, when used in treating mice with intracranial glioblastoma (GBM) xenografts. Approaches used in this investigation include: bioluminescence imaging (BLI) for monitoring intracranial tumor growth and response to therapy; determination of survival benefit from treatment; analysis of tumor IHC reactivity for indication of treatment effect on proliferation and apoptotic response; Western blot analysis for determination of effects of treatment on ERBB and ERBB signaling mediator activation; and high-performance liquid chromatography for determination of NT113 concentration in tissue extracts from animals receiving oral administration of inhibitor. Our results show that NT113 is active against GBM xenografts in which wild-type EGFR or EGFRvIII is highly expressed. In experiments including lapatinib and/or erlotinib, NT113 treatment was associated with the most substantial improvement in survival, as well as the most substantial tumor growth inhibition, as indicated by BLI and IHC results. Western blot analysis results indicated that NT113 has inhibitory activity, both in vivo and in vitro, on ERBB family member phosphorylation, as well as on the phosphorylation of downstream signaling mediator Akt. Results from the analysis of animal tissues revealed significantly higher NT113 normal brain-to-plasma and intracranial tumor-to-plasma ratios for NT113, relative to erlotinib, indicating superior NT113 partitioning to intracranial tissue compartments. These data provide a strong rationale for the clinical investigation of NT113, a novel ERBB inhibitor, in treating patients with GBM. Mol Cancer Ther; 13(12); 2919–29. ©2014 AACR.
Can Anti-AQP4 Antibody Damage the Blood-Brain Barrier?
Authors: Akaza Miho , Tanaka Keiko , Tanaka Masami , Sekiguchi Teruhiko , Misawa Tamako , Nishina Kazutaka , Kawachi Izumi , Nishizawa Masatoyo , Mizusawa Hidehiro , Yokota Takanori
Published: October 2014

Background: Aquaporin 4 (AQP4) is a water-channel protein predominantly expressed in astrocyte end feet that make up the blood-brain barrier (BBB). Recently, anti-AQP4 antibody has been identified as a specific biomarker of neuromyelitis optica (NMO). However, whether anti-AQP4 antibodies damage the BBB is unclear. Methods: We evaluated BBB damage in patients with NMO and multiple sclerosis by measuring albumin leakage (AL) and studied its correlation with anti-AQP4 antibody. Results: No obvious difference in AL was observed between patients with and without anti-AQP4 antibodies. In the multivariate analysis, anti-AQP4 antibody was not associated with BBB damage. Of the anti-AQP4-positive patients, 58.0% had normal AL values, and the degree of BBB damage was unrelated to the anti-AQP4 antibody titer. In addition, 41.9% of anti-AQP4-positive patients showed no gadolinium enhancement of the MRI. Conclusion: These results indicate that the presence of anti-AQP4 antibody alone in plasma is insufficient to disrupt the BBB.
Up-Front Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Arising from the Myelodysplastic Syndrome
Authors: Choi Yunsuk , Kim Sung-Doo , Park Young-Hoon , Lee Jae Seok , Kim Dae-Young , Lee Jung-Hee , Lee Kyoo-Hyung , Seol Miee , Lee Young-Shin , Kang Young-Ah , Jeon Mijin , Jung Ah Rang , Lee Je-Hwan
Published: October 2014

In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available. © 2014 S. Karger AG, Basel
Targeting Individuals with Problematic Alcohol Use via Web-Based Cognitive-Behavioral Self-Help Modules, Personalized Screening Feedback or Assessment Only: A Randomized Controlled Trial
Authors: Sinadinovic Kristina , Wennberg Peter , Johansson Magnus , Berman Anne H.
Published: October 2014

Background/Aims: Most problematic alcohol users never seek professional help to reduce their use, and Web-based interventions might fulfill users' unmet needs for professional support. Methods: This randomized controlled trial compared two open Web-based interventions, one extended self-help program and one brief screening and feedback intervention, with an assessment-only control group. Participants were 633 Internet help seekers with at least hazardous alcohol use (Alcohol Use Disorders Identification Test, AUDIT ≥6 for women and ≥8 for men). Results: All groups reduced their alcohol use at 3-month follow-up (p < 0.001), remaining stable at the 6- and 12-month follow-ups (n.s.) according to AUDIT-C and AUDIT scores (intention-to-treat, ITT, analysis). Per protocol (PP) analysis, including only participants who accessed the interventions and also reported accessing additional outside interventions during the trial, showed that about 75% of extended self-help participants moved from probable dependence, harmful or hazardous use to lower alcohol use levels at 3- and 6- and 12-month follow-ups, compared to about 40-60% of brief intervention users and controls who accessed extra help (p < 0.05). Conclusion: ITT analysis suggested parity over time for all interventions, including assessment only, in reducing problematic alcohol use. In contrast, PP analysis suggested that cognitive-behavioral extended self-help in combination with other interventions was more effective in changing alcohol use than brief intervention or assessment only.
Glycemic Pattern in Diabetic Patients on Hemodialysis: Continuous Glucose Monitoring (CGM) Analysis
Authors: Gai Massimo , Merlo Ilenia , Dellepiane Sergio , Cantaluppi Vincenzo , Leonardi Gianluca , Fop Fabrizio , Guarena Cesare , Grassi Giorgio , Biancone Luigi
Published: October 2014

Background/Aims: Recent evidences suggest that hemodialysis (HD) induces glycemic variations in diabetic patients. Continuous glucose monitoring (CGM) devices measure interstitial glucose in a ‘Holter-like' manner thereby improving the glycemic control assessment method. Methods: A CGM device (Medtronic iPRO) was used on 12 diabetic patients with chronic HD for 6 days to assess intra- and extra-dialytic interstitial glucose. Results: In all enrolled patients, HD was associated with a decrease of interstitial glucose values. Intradialytic glucose nadir was 79 mg/dl and it was reached at the third hour after the beginning of the session. At the end of HD, interstitial glucose increased in all patients and a glycemic peak (187 mg/dl) occurred after an average time of 2.5 h. No episodes of nocturnal hypoglycemia occurred. Conclusion: HD is associated with significant intradialytic reduction of glycemia and postdialytic hyperglycemia. CGM devices result in better monitoring of glycemic trends in diabetic patients on chronic HD and could improve insulin management.
Reversion by Vitamin E Treatment of the Oxidative Damage but Not of the Advancement in Reproductive Senescence Produced by Neonatal Hypoxia or Hypoxia-Ischemia in Female Rats
Authors: Ezquer Marcelo E. , Valdez Susana R. , Seltzer Alicia M. , Jahn Graciela A.
Published: October 2014

Background/Aims: Few studies address the long-term consequences of perinatal hypoxia (H), a frequent birth complication. Previously we described advanced reproductive senescence (premature loss of regular cyclicity) in female rats subjected to perinatal H or H plus unilateral ischemia (HI) associated with changes in the hypothalamic expression of estrogen and opioid receptors. Our aim is to explore whether hypothalamic inflammation and oxidative damage mediate these reproductive alterations. Methods: Female rats were subjected on postnatal day (PND) 7 to H (6.5% O2 for 50 min) or HI (H + right carotid artery ligature) and inflammation/oxidative damage markers, such as iNOS, nNOS, insulin-like growth factor (IGF) system expression, glial reaction and macrophage invasion in the medial basal hypothalamus-preoptic area (GFAP Western blot and immunohistochemistry, ED1 immunohistochemistry), were determined. The effect of antioxidant treatment with vitamin E (VE; 1.5 mg/rat on PND 4, 6 and 8) was also explored. Results: No significant cellular inflammatory reactions were observed although GFAP protein was significantly increased at early times after injury. Forty-eight hours after injury iNOS, nNOS and IGF-I mRNA decreased in the HI group, and nNOS in the H group. IGFBP-3 mRNA increased in HI rats at 48 h and 30 days, while it fell at 7 days postinjury in both groups. VE treatment prevented the effects of HI on oxidation/inflammation markers, but did not prevent the premature onset of reproductive senescence or the altered hormone receptors expression. Conclusion: These results suggest that the oxidative and inflammatory damage caused by perinatal H or HI may not be responsible for the late-onset reproductive abnormalities.
Intra-Arterial Signal on Arterial Spin Labeling Perfusion MRI to Identify the Presence of Acute Middle Cerebral Artery Occlusion
Authors: Tada Yoshiteru , Satomi Junichiro , Abe Takashi , Kuwayama Kazuyuki , Sogabe Shu , Fujita Koji , Yamamoto Nobuaki , Kaji Ryuji , Harada Masafumi , Nagahiro Shinji
Published: October 2014

Background: The susceptibility vessel sign on gradient echo-type-T2*-weighted imaging is a well-known marker of arterial occlusion. Stagnant flow in front of the middle cerebral artery (MCA) occlusion sites may contribute to the intra-arterial, high-intensity signal on arterial spin labeling magnetic resonance imaging (MRI), making it another potential marker of MCA occlusion. We compared the intra-arterial, high-intensity signal and susceptibility vessel sign in patients with symptomatic MCA occlusion and patients without major vessel occlusion. Methods: We identified transient ischemic attack or ischemic stroke patients with (1) 3-T MRI performed within 24 h after clinical onset including arterial spin labeling, T2*-weighted imaging, and magnetic resonance angiography (MRA) and (2) either having MCA occlusion (n = 34 patients) or without major vessel occlusion (n = 24 patients). The intra-arterial, high-intensity signal was defined as an enlarged circular or linear bright hyperintensity within the artery. The susceptibility vessel sign was defined as an enlarged spot of hypointensity within the MCA, in which the diameter of the hypointense signal within the vessel exceeded the contralateral vessel diameter. The presence or absence of the intra-arterial, high-intensity signal and susceptibility vessel sign were assessed, along with their inter-rater agreement and consistency with the presence of MCA occlusion on MRA. Results: The intra-arterial, high-intensity signal was detectable in 30 patients (52%), and susceptibility vessel sign was observed in 17 patients (29%). The sensitivity of the intra-arterial high-intensity signal was significantly higher than that of the susceptibility vessel sign (88% vs. 50%; p < 0.05). The accuracy of the intra-arterial high-intensity signal was also higher than that of the susceptibility vessel sign (93% vs. 71%; p < 0.05). The intra-arterial high-intensity signal was situated in the proximal regions of the susceptibility vessel sign on T2*WI within the MCA. Neither the intra-arterial high-intensity signal nor the susceptibility vessel sign was observed in patients without major vessel occlusion. Inter-rater agreement was good for intra-arterial high-intensity signal detection (κ = 0.73) and moderate for susceptibility vessel sign detection (κ = 0.47). The presence or absence of the intra-arterial high-intensity signal was highly consistent with that of MCA occlusion on MRA (κ = 0.74). Conclusions: The intra-arterial high-intensity signal on arterial spin labeling appears to be useful to identify the presence of acute MCA occlusion and may be associated with stagnant flow in front of occlusion sites. The intra-arterial high-intensity signal may also be used to identify the occlusion site.
Autoantibodies against β1 Receptor and AT1 Receptor in Type 2 Diabetes Patients with Left Ventricular Dilatation
Authors: Zhao Linshuang , Xu Chunyan , Xu Jinling
Published: October 2014

Objectives: To explore the relationship between the autoantibodies against the β1 and AT1 receptors and left ventricular dilatation in patients with type 2 diabetes (T2DM). Methods: The autoantibodies against the β1 and angiotensin II type 1 (AT1) receptors of T2DM patients with and without hypertension were screened by ELISA. Multiple logistic regression was used to analyze the risk factors for left ventricular dilatation. The reversing effect of left ventricular dilatation was evaluated after receptor blocker treatment. Results: The positive rates of autoantibodies against the β1 and AT1 receptors (43.0 and 44.1%, respectively) in T2DM patients with hypertension were significantly higher than those in normotensive patients (16.0 and 10.4%, respectively; all p < 0.01). Furthermore, among T2DM patients with hypertension, the positive rates (61.4 and 64.9%, respectively) in patients with left ventricular dilatation were remarkably higher than those with normal left ventricular dimensions (34.4 and 36.1%, respectively; all p < 0.01). The presence of β1 receptor antibody and AT1 receptor antibody were risk factors for left ventricular dilatation (p < 0.05). The curative effect of metoprolol tartrate and valsartan in reversing left ventricular hypertrophy in the group positive for autoantibodies was much better than in the negative group. Conclusion: The findings show that autoantibodies against the β1 and AT1 receptors may play a role in predicting left ventricular dilatation in T2DM patients in combination with hypertension. Metoprolol tartrate and valsartan are effective and safe in the treatment of these patients.
Ramipril Lowers Plasma FGF-23 in Patients with Diabetic Nephropathy
Authors: Yilmaz Mahmut Ilker , Sonmez Alper , Saglam Mutlu , Kurt Yasemin Gulcan , Unal Hilmi Umut , Karaman Murat , Gok Mahmut , Cetinkaya Hakki , Eyileten Tayfun , Oguz Yusuf , Vural Abdulgaffar , Mallamaci Francesca , Zoccali Carmine
Published: October 2014

Background/Aims: Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition. Methods: In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32). Results: Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage. Conclusion: Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).
The Rhesus Site
Authors: Wagner Franz F. , Flegel Willy A.
Published: October 2014

The Rhesus Site is a resource for information of the ‘Rhesus' blood group. It is intended for specialists and non-specialists. The website details research in the field relevant for transfusion medicine, immunohematology, and molecular research. Link areas guide to important publications and to methodological resources for Rhesus. Many data originally presented at The Rhesus Site have been formally published later. The ‘RhesusBase' section represents the largest database for RHD alleles; the ‘RhesusSurveillance' section details the results of the largest prospective observational study on anti-D immunization events in D-positive patients. Visitors to the website are encouraged to explore the intricacies of the most complex blood group gene locus.
Fetuin A/Nutritional Status Predicts Cardiovascular Outcomes and Survival in Hemodialysis Patients
Authors: Chen Hung-Yuan , Chiu Yen-Ling , Hsu Shih-Ping , Pai Mei-Fen , Yang Ju-Yeh , Peng Yu-Sen
Published: October 2014

Background: Fetuin A - a predictor of cardiovascular (CV) outcomes in dialysis patients - is correlated with over-nutrition in the general population. Whether fetuin A and nutritional status interact with each other to alter CV outcomes and survival in hemodialysis (HD) patients remains unknown. Methods: We performed a prospective study on 388 prevalent HD patients. We used the geriatric nutritional risk index (GNRI) for the evaluation of nutritional status. Study outcomes included the occurrence of CV event, CV death, and all-cause mortality during follow-up; interactions between parameters for predicting outcomes were assessed by the interaction terms in a Cox regression model. Results: Overall, 131 patients experienced CV events and 92 patients died, with 51 CV deaths. HD patients with higher fetuin A levels had lower numbers of CV events (adjusted hazard ratio [HR], 0.9; 0.81-0.99) and all-cause mortality (adjusted HR, 0.97; 0.91-0.99). However, patients with higher GNRI had lower all-cause mortality (adjusted HR, 0.79; 0.51-0.98, for every 10-unit increase). Fetuin A levels and GNRI showed a significant interaction in the prediction of CV events (adjusted HR, 1.01; 1.008-1.02) but not for all-cause or CV mortality. In patients with poor nutritional status, higher fetuin A levels were associated with fewer CV events; however, in contrast, in subjects with better nutritional status, higher fetuin A levels appeared to lead to a higher number of CV events. Conclusions: Fetuin A showed a remarkable interaction with nutritional status in evaluating the risks of CV morbidities in prevalent HD patients.
Worse In-Hospital Outcomes in Patients with Transient Ischemic Attack in Association with Acute Kidney Injury: Analysis of Nationwide In-Patient Sample
Authors: Saeed Fahad , Adil Malik M. , Malik Ahmed A. , Qureshi Mushtaq H. , Nahab Fadi
Published: October 2014

Objectives: The effect of acute kidney injury (AKI) on outcomes of transient ischemic attack (TIA) is largely unknown. We wanted to determine the impact of AKI on the outcomes of patients admitted with TIA. Methods: Data from all adult patients admitted to the U.S. hospitals between 2005 and 2011 with a primary discharge diagnosis of TIA and secondary diagnosis of AKI were included, using the nationwide in-patient dataset. The association of AKI with TIA-related mortality and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis. Results: Of the 1,173,340 patients admitted with TIA, 45,974 (3.8%) had AKI. Dialysis was required in 29 (0.06%) patients. TIA patients with AKI had higher rates of moderate-to-severe disability (21.2 vs. 13.7%, p ≤ 0.0001), and in-hospital mortality (0.6 vs. 0.1%, p ≤ 0.0001) compared with those without AKI. After adjusting for age, sex, and potential confounders; TIA patients with AKI had higher odds of moderate-to-severe disability [OR 1.3, 95% CI 1.2-1.4, p < 0.0001] and death (OR 4.2, 95% CI 3.0-6.1, p < 0.0001). Conclusions: AKI in patients with TIA is associated with significantly higher rates of moderate-to-severe disability at discharge and in-hospital mortality compared with those without AKI.
Repeated Negative Biopsies in Isolated High-Grade Cystic Duct Dysplasia with Progression to Adenocarcinoma
Authors: Sunkel-Laing Benjamin , Kalam Abdul , Renfrew Ian , Mears Lisa , Kocher Hemant M.
Published: October 2014

Cystic and bile duct dysplasia is a rare histological finding, especially when found in the absence of an underlying malignancy. We report a patient who presented with jaundice and weight loss. Clinical and cytological evidence suggested a diagnosis of cholangiocarcinoma and the patient underwent a pancreatico-duodenectomy. Histopathological examination suggested a diagnosis of two foci of biliary dysplasia: cystic duct and lower common bile duct. Fifteen months later, the patient re-presented with signs of obstructive jaundice and biliary sepsis. Although CT scan revealed images highly indicative of metastatic disease, repeated biopsies failed to confirm this. Eventually a liver biopsy did reveal moderately differentiated adenocarcinoma, however oncological interventional was no longer appropriate and the patient was managed palliatively. This case report focuses on the current understanding of progression of biliary dysplasia.
Accessory Pancreatic Duct-Portal Vein Fistula: A Rare Complication of Chronic Pancreatitis during Endoscopic Retrograde Cholangiopancreatography
Authors: Kawaguchi Yoshiaki , Lin Jung-Chun , Kawashima Yohei , Maruno Atsuko , Ito Hiroyuki , Ogawa Masami , Mine Tetsuya
Published: October 2014

Pancreatitis, hemorrhage and perforation are the most frequent complications associated with endoscopic retrograde cholangiopancreatography (ERCP). We report a rare case of accessory pancreatic duct-portal vein fistula, which occurred during ERCP in a patient with chronic pancreatitis. To our knowledge, this is the first report of accessory pancreatic duct-portal vein fistula created during ERCP by the use of a guide wire.
Predicting the Effects of Blood Pressure–Lowering Treatment on Major Cardiovascular Events for Individual Patients With Type 2 Diabetes Mellitus
Authors: van der Leeuw Joep , Visseren Frank L.J. , Woodward Mark , Zoungas Sophia , Kengne Andre Pascal , van der Graaf Yolanda , Glasziou Paul , Hamet Pavel , MacMahon Stephen , Poulter Neil , Grobbee Diederick E. , Chalmers John
Published: October 2014

Abstract—

Blood pressure–lowering treatment reduces cardiovascular risk in patients with diabetes mellitus, but the effect varies between individuals. We sought to identify which patients benefit most from such treatment in a large clinical trial in type 2 diabetes mellitus. In Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) participants (n=11 140), we estimated the individual patient 5-year absolute risk of major adverse cardiovascular events with and without treatment by perindopril–indapamide (4/1.25 mg). The difference between treated and untreated risk is the estimated individual patient’s absolute risk reduction (ARR). Predictions were based on a Cox proportional hazards model inclusive of demographic and clinical characteristics together with the observed relative treatment effect. The group-level effect of selectively treating patients with an estimated ARR above a range of decision thresholds was compared with treating everyone or those with a blood pressure >140/90 mm Hg using net benefit analysis. In ADVANCE, there was wide variation in treatment effects across individual patients. According to the algorithm, 43% of patients had a large predicted 5-year ARR of ≥1% (number-needed-to-treat [NNT
5
] ≤100) and 40% had an intermediate predicted ARR of 0.5% to 1% (NNT
5
=100–`200). The proportion of patients with a small ARR of ≤0.5% (NNT
5
≥200) was 17%. Provided that one is prepared to treat at most 200 patients for 5 years to prevent 1 adverse outcome, prediction-based treatment yielded the highest net benefit. In conclusion, a multivariable treatment algorithm can identify those individuals who benefit most from blood pressure–lowering therapy in terms of ARR of major adverse cardiovascular events and may be used to guide treatment decisions in individual patients with diabetes.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00145925.
Role of In Vivo Vascular Redox in Resistance Arteries
Authors: Hilgers Rob H.P. , Das Kumuda C.
Published: October 2014

Vascular thiol redox state has been shown to modulate vasodilator functions in large conductance Ca
2+
-activated K
+
channels and other related channels. However, the role of vascular redox in small resistance arteries is unknown. To determine how in vivo modulation of thiol redox state affects small resistance arteries relaxation, we generated a transgenic mouse strain that overexpresses thioredoxin, a small redox protein (Trx-Tg), and another strain that is thioredoxin-deficient (dnTrx-Tg). The redox state of the mesenteric arteries (MAs) in Trx-Tg mice is found to be predominantly in reduced state; in contrast, MAs from dnTrx-Tg mice remain in oxidized state. Thus, we created an in vivo redox system of mice and isolated the second-order branches of the main superior MAs from wild-type, Trx-Tg, or dnTrx-Tg mice to assess endothelium-dependent relaxing responses in a wire myograph. In MAs isolated from Trx-Tg mice, we observed an enhanced intermediate-conductance Ca
2+
–activated potassium channel contribution resulting in a larger endothelium-dependent hyperpolarizing (EDH) relaxation in response to indirect (acetylcholine) and direct (NS309) opening of endothelial calcium-activated potassium channels. MAs derived from dnTrx-Tg mice showed both blunted nitric oxide–mediated and EDH-mediated relaxation compared with Trx-Tg mice. In a control study, diamide decreased EDH relaxations in MAs of wild-type mice, whereas dithiothreitol improved EDH relaxations and was able to restore the diamide-induced impairment in EDH response. Furthermore, the basal or angiotensin II–mediated systolic blood pressure remained significantly lower in Trx-Tg mice compared with wild-type or dnTrx-Tg mice, thus directly establishing redox-mediated EDH in blood pressure control.
“At War with Israel”: East Germany’s Key Role in Soviet Policy in the Middle East
Authors: Herf Jeffrey
Published: October 2014

The Middle East was one of the crucial battlefields of the global Cold War between the Soviet Union and the West; it was also a region in which East Germany played a salient role in the Soviet bloc’s antagonism toward Israel. From 1953, when the German Democratic Republic (GDR) signed its first trade agreement with Egypt, until 1989, when the Communist regime in the GDR collapsed, East Germany opposed the state of Israel and supported Israel’s enemies in the Arab world, providing arms, training, and other support to countries and terrorist groups that sought to destroy Israel. From the mid-1960s until 1989, but especially from 1967 to the mid-1980s, both the Soviet Union and the GDR were in an undeclared state of war against Israel.
Dissonant Voices: Soviet Youth Mobilization and the Cuban Missile Crisis
Authors: Kozovoi Andrei
Published: October 2014

Although studies of the Cuban missile crisis abound, the story “from below” of those fateful days of October 1962 remains largely to be written. This is particularly true for the Soviet side. Little is known about the way the Soviet population, and particularly youth, the prime category for propaganda, perceived what is widely regarded as the most dangerous crisis of the Cold War. Youth were indeed the target of a massive mobilization campaign, but one that was ridden with many shortcomings, or, using the musical metaphor, dissonances. The propaganda machine (mainly the press but also radio and film) had been cultivating anti-Americanism and solidarity with the Cuban people for quite some time, but when the crisis suddenly arose, many “choir members” were unable to modulate their voice to the right key, if there ever was one. Secrecy and improvisation in the Communist Party’s highest organs, coupled with the trauma of World War II, bore the fruits of inertia, formalism, pacifism, and above all, embarrassed silence, eventually contributing to an extreme and often ambivalent palette of reactions.
The Defeated of the Greek Civil War: From Fighters to Political Refugees in the Cold War
Authors: Karpozilos Kostis
Published: October 2014

In the fall of 1949, after the end of the Greek Civil War, the bulk of the defeated Greek Communist (KKE) fighters were covertly transported from Albania to Soviet Uzbekistan. This article addresses the covert relocation project, organized by the Soviet Communist Party, and the social engineering program intended to create a prototype Greek People’s Democracy in Tashkent. Drawing on Soviet and Greek Communist Party records, the article raises three major issues: first, the contingencies of postwar transition in the Balkans and the precarious status of the Albanian regime; second, the international Communist response to the military defeat of the KKE in 1949 and the competing visions of the Greek, Soviet, and Albanian parties regarding the future of the Democratic Army of Greece (DAG); third, the intentions of the KKE to establish military bases in Albania and the party’s ensuing effort to transform the agrarian fighters of the DAG into revolutionary cadres for a future victorious repatriation in Greece. Drawing these elements together, the article elucidates the relocation operation of 1949, positions the Greek political refugee experience within the postwar “battle of refugees,” and challenges the widespread historiographical assumption that the KKE immediately abandoned the prospect of a renewed armed confrontation.
Spectrums of Oppression: Gender and Sexuality during the Cold War
Authors: Dumančić Marko
Published: October 2014

This article reviews the scholarship on Cold War sexuality issues prior to the 1969 Stonewall riots, paying particular attention to recent books by Robert J. Corber, Michael S. Sherry, and Jennifer V. Evans. The Cold War in the West affected both the lived and the discursive realities of sexual minorities in a paradoxical way. On the one hand, anxieties about the superpower rivalry facilitated regulatory frameworks and social demarcation lines that profoundly circumscribed the agency of lesbian, gay, bisexual, and transgender groups and individuals. On the other hand, these borders and regulatory systems often backfired, subverted their intended function, or simply produced unintended consequences. Although repression of non-normative sexual and gender identities remained a fact of life during the first two-and-a half decades of the Cold War, it does not reveal the totality of the Cold War experience. The current research on Cold War sexualities demonstrates that Cold War culture can thus be best understood as a complex system in which fissures and breaks were as salient as the demand for uniformity and control.
Reinstatement of Individual Past Events Revealed by the Similarity of Distributed Activation Patterns during Encoding and Retrieval
Authors: Wing Erik A. , Ritchey Maureen , Cabeza Roberto
Published: October 2014

Neurobiological memory models assume memory traces are stored in neocortex, with pointers in the hippocampus, and are then reactivated during retrieval, yielding the experience of remembering. Whereas most prior neuroimaging studies on reactivation have focused on the reactivation of sets or categories of items, the current study sought to identify cortical patterns pertaining to memory for individual scenes. During encoding, participants viewed pictures of scenes paired with matching labels (e.g., “barn,” “tunnel”), and, during retrieval, they recalled the scenes in response to the labels and rated the quality of their visual memories. Using representational similarity analyses, we interrogated the similarity between activation patterns during encoding and retrieval both at the item level (individual scenes) and the set level (all scenes). The study yielded four main findings. First, in occipitotemporal cortex, memory success increased with encoding-retrieval similarity (ERS) at the item level but not at the set level, indicating the reactivation of individual scenes. Second, in ventrolateral pFC, memory increased with ERS for both item and set levels, indicating the recapitulation of memory processes that benefit encoding and retrieval of all scenes. Third, in retrosplenial/posterior cingulate cortex, ERS was sensitive to individual scene information irrespective of memory success, suggesting automatic activation of scene contexts. Finally, consistent with neurobiological models, hippocampal activity during encoding predicted the subsequent reactivation of individual items. These findings show the promise of studying memory with greater specificity by isolating individual mnemonic representations and determining their relationship to factors like the detail with which past events are remembered.