bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Pain in the Emergency Department
Authors: Thomas Stephen H.
Published: May 2013

Since pain is a primary impetus for patient presentation to the Emergency Department (ED), its treatment should be a priority for acute care providers. Historically, the ED has been marked by shortcomings in both the evaluation and amelioration of pain. Over the past decade, improvements in the science of pain assessment and management have combined to facilitate care improvements in the ED. The purpose of this review is to address selected topics within the realm of ED pain management. Commencing with general principles and definitions, the review continues with an assessment of areas of controversy and advancing knowledge in acute pain care. Some barriers to optimal pain care are discussed, and potential mechanisms to overcome these barriers are offered. While the review is not intended as a resource for specific pain conditions or drug information, selected agents and approaches are mentioned with respect to evolving evidence and areas for future research.
Inhibition of LXRα/SREBP-1c-Mediated Hepatic Steatosis byJiang-ZhiGranule
Authors: Wang Miao , Sun Shanshan , Wu Tao , Zhang Li , Song Haiyan , Hao Weiwei , Zheng Peiyong , Xing Lianjun , Ji Guang
Published: May 2013

Nonalcoholic fatty liver (NAFL) is increasingly recognized as one of the most common causes of chronic liver disease worldwide. Traditional Chinese medicine (TCM), as the alternative and complementary medicine, may provide some profound health benefit. “Jiang-Zhi” Granule (JZG) was composed based on TCM pathogenesis of NAFL: the retention of inner dampness, heat and blood stasis. This study investigated effects of JZG on liver X receptor-α(LXRα)/sterol regulatory element binding protein-1c (SREBP-1c) pathway in high-fat-diet-(HFD-)induced hepatic steatosis, as well as in free-fatty-acid-(FFA-)and T0901317-treated HepG2 cells. The results showed that JZG had an antisteatotic effect on HFD-fed rats. JZG decreased the activation of SREBP-1c through inhibiting LXRα-mediated SREBP-1c transcription, as well as through inhibiting the maturation of SREBP-1c independent of LXRα. These findings may provide molecular evidence for the use of JZG as a promising therapeutic option for NAFL and support us to continue JZG treatment in NAFL. For JZG treatment to be widely accepted, a randomized, double-blind, multicenter, placebo-controlled, phase III trial is ongoing.
The Effects of Chlormadinone Acetate on Lower Urinary Tract Symptoms and Erectile Functions of Patients with Benign Prostatic Hyperplasia: A Prospective Multicenter Clinical Study
Authors: Fujimoto Kiyohide , Hirao Yoshihiko , Ohashi Yasuo , Shibata Yasuhiro , Fuji Kohzo , Tsuji Hidenori , Miyazawa Katsuhito , Ohtani Mikinobu , Furuya Ryoji , Boku Eitetsu
Published: May 2013

Purpose. To evaluate the effects of chlormadinone acetate (CMA), progesterone-derived antiandrogen, on lower urinary tract symptoms (LUTS) and erectile functions of benign prostatic hyperplasia (BPH).Methods.A multicenter, single-cohort prospective study was conducted. A total of 114 patients received CMA for 16 weeks. The endpoints were changes in International Prostate Symptom Scores (IPSS), IPSS-QOL, International Index of Erectile Function-5,Qmaxprostate volume, and residual urine volume.Results.Significant improvements were observed in IPSS from week 8 to week 48 (32 weeks after treatment). IPSS-QOL improvements were also significant from week 8 to week 48.Qmaxincreased to a maximum at Week 16 and remained elevated throughout the study. Moreover, a decrease of 25% in prostate volume was observed at Week 16. IPSS, QOL, and Qmax changes during the study were not different between the previously treated and untreated patients. IPSS storage subscore changes differed between the age groups. Few severe adverse reactions were observed, except for erectile dysfunction.Conclusions.CMA rapidly and significantly reduced prostate volume and improved voiding and storage symptoms and QOL. Our results suggest that CMA is safe and beneficial, especially for elderly patients with LUTS associated with BPH.
Magmatism in the Asunción-Sapucai-Villarrica Graben (Eastern Paraguay) Revisited: Petrological, Geophysical, Geochemical, and Geodynamic Inferences
Authors: Comin-Chiaramonti Piero , De Min Angelo , Cundari Aldo , Girardi Vicente A. V. , Ernesto Marcia , Gomes Celso B. , Riccomini Claudio
Published: May 2013

The Asunción-Sapucai-Villarrica graben (ASV) in Eastern Paraguay at the westernmost part of the Paraná Basin was the site of intense magmatic activity in Mesozoic and Tertiary times. Geological, petrological, mineralogical, and geochemical results indicate that the following magmatic events are dominant in the area: (1) tholeiitic basalt and basaltic andesites, flows and sills of low- and high-titanium types; (2) K-alkaline magmatism, where two suites are distinguished, that is, basanite to phonolite and alkali basalt to trachyte and their intrusive analogues; (3) ankaratrite to phonolite with strong Na-alkaline affinity, where mantle xenoliths in ultramafic rocks are high- and low-potassium suites, respectively. The structural and geophysical data show extensional characteristics for ASV. On the whole, the geochemical features imply different mantle sources, consistently with Sr-Nd isotopes that are Rb-Nd enriched and depleted for the potassic and sodic rocks, respectively. Nd model ages suggest that some notional distinct “metasomatic events” may have occurred during Paleoproterozoic to Neoproterozoic times as precursor to the alkaline and tholeiitic magmas. It seems, therefore, that the genesis of the ASV magmatism is dominated by a lithospheric mantle, characterized by small-scale heterogeneity.
Application of an Integrated Model with MCDM and IPA to Evaluate the Service Quality of Transshipment Port
Authors: Chou Chien-Chang , Ding Ji-Feng
Published: May 2013

It is often to solve complex decision-making problems in the marine transportation environment, such as the evaluation of service quality and the location choice of ports. In this paper, an integrated model with multiple-criteria decision making (MCDM) and importance-performance analysis (IPA) is presented and then is applied to solve the problem of service quality evaluation of transshipment port. The MCDM approach can be used to deal with both quantitative data and qualitative ratings simultaneously. The IPA approach can be applied to realize the shortcomings of service quality of ports and rank the ranking of strategies for improving service quality of transshipment port. Finally, some useful suggestions for improving the service quality of ports are given in the paper.
Brazilian Propolis Antileishmanial and Immunomodulatory Effects
Authors: da Silva Suelen Santos , Thomé Graciele da Silva , Cataneo Allan Henrique Depieri , Miranda Milena Menegazzo , Felipe Ionice , Andrade Célia Guadalupe Tardeli de Jesus , Watanabe Maria Angélica Ehara , Piana Gilce Maria , Sforcin José Maurício , Pavanelli Wander Rogério , Conchon-Costa Ivete
Published: May 2013

The antileishmanial and immunomodulatory effects of propolis collected in Botucatu, São Paulo State, Brazil, were evaluated inLeishmania (Viannia) braziliensisexperimental infection. The antileishmanial effect of propolis on promastigote forms was verified by reducing growth and by promoting morphologic alterations observed by scanning electron microscopy. Inin vitroimmunomodulatory assays, macrophages were pretreated with propolis and then infected withL. (V.) braziliensis.In vivo, supernatants from liver cells and peritoneal exudate of BALB/c mice pretreated with propolis and infected withLeishmania(107/mL promastigotes) were collected, and TNF-αand IL-12 were measured by ELISA. Macrophages incubated with propolis showed a significant increase in interiorization and further killing of parasites. An increased TNF-αproduction was seen in mice pretreated with propolis, whereas IL-12 was downregulated during the infection. In conclusion, Brazilian propolis showed a direct action on the parasite and displayed immunomodulatory effects on murine macrophages, even though the parasite has been reported to affect the activation pathways of the cell. The observed effects could be associated with the presence of phenolic compounds (flavonoids, aromatic acids, and benzopyranes), di- and triterpenes, and essential oils found in our propolis sample.
Natural History of the Bruise: Formation, Elimination, and Biological Effects of Oxidized Hemoglobin
Authors: Jeney Viktória , Eaton John W. , Balla György , Balla József
Published: May 2013

Numerous disease states are associated with hemolysis or hemorrhage. Because red cells in the extravascular space tend to lyse quickly, hemoglobin (Hb) is released and is prone to autoxidation producing MetHb. Inorganic and organic peroxides may convert Hb and MetHb to higher oxidation states such as ferrylHb. FerrylHb is not a single chemical entity but is a mixture of globin- and porphyrin-centered radicals and covalently cross-linked Hb multimers. Oxidized Hb species are potent prooxidants caused mainly by heme release from oxidized Hb. Moreover, ferrylHb is a strong proinflammatory agonist that targets vascular endothelial cells. This proinflammatory effect of ferrylHb requires actin polymerization, is characterized by the upregulation of proinflammatory adhesion molecules, and is independent of heme release. Deleterious effects of native Hb are controlled by haptoglobin (Hp) that binds cell-free Hb avidly and facilitates its removal from circulation through the CD163 macrophage scavenger receptor-mediated endocytosis. Under circumstances of Hb oxidation, Hp can prevent heme release from MetHb, but unfortunately the Hp-mediated removal of Hb is severely compromised when Hb is structurally altered such as in ferrylHb allowing deleterious downstream reactions to occur even in the presence of Hp.
An Entropy-Based Model for Basal Ganglia Dysfunctions in Movement Disorders
Authors: Darbin Olivier , Dees Daniel , Martino Anthony , Adams Elizabeth , Naritoku Dean
Published: May 2013

During this last decade, nonlinear analyses have been used to characterize the irregularity that exists in the neuronal data stream of the basal ganglia. In comparison to linear parameters for disparity (i.e., rate, standard deviation, and oscillatory activities), nonlinear analyses focus on complex patterns that are composed of groups of interspike intervals with matching lengths but not necessarily contiguous in the data stream. In light of recent animal and clinical studies, we present a review and commentary on the basal ganglia neuronal entropy in the context of movement disorders.
Quo Vadis Radiotherapy? Technological Advances and the Rising Problems in Cancer Management
Authors: Allen Barry J. , Bezak Eva , Marcu Loredana G.
Published: May 2013

Purpose. Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival.Methods. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted.Results. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease.Conclusion. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.
Cerebral Wegener’s Granuloma: Surgery Mandatory for Diagnosis and Treatment
Authors: Nicolosi Federico , Nodari Giovanni , Spena Giannantonio , Roca Elena , Migliorati Karol , Esposito Giacomo , Stefini Roberto , Fontanella Marco , Panciani Pier Paolo
Published: May 2013

The involvement of the central nervous system in case of Wegener granulomatosis (WG) is infrequent and usually leads to cranial nerve abnormalities, cerebrovascular events, and seizures. Meningeal involvement is quite rare and usually is due to the spreading from adjacent disease in the skull base. We described the case of a remote intraparenchymal Wegener’s granuloma in a 55-year-old man presenting with seizures and a history of severe generalized WG. The radiological findings were not useful for the diagnosis, and the pharmacological treatment was ineffective. The importance of a surgery in case of localized WG has been emphasized, in order to confirm the diagnosis and to avoid additional medicaments, like antiepileptic drugs, potentially harmful in immunosuppressed patients.
Contribution of CFTR to Alveolar Fluid Clearance by Lipoxin A4via PI3K/Akt Pathway in LPS-Induced Acute Lung Injury
Authors: Yang Yi , Cheng Yang , Lian Qing-Quan , Yang Li , Qi Wei , Wu De-Rong , Zheng Xia , Liu Yong-Jian , Li Wen-Juan , Jin Sheng-Wei , Smith Fang Gao
Published: May 2013

The lipoxins are the first proresolution mediators to be recognized and described as the endogenous “braking signals” for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4significantly improved histology of rat lungs and inhibited IL-6 and TNF-αin LPS-induced lung injury. In addition, lipoxin A4increased alveolar fluid clearance (AFC) and the effect of lipoxin A4on AFC was abolished byCFTRinh-172(a specific inhibitor of CFTR). Moreover, lipoxin A4could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expressionin vitroandin vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4may provide a potential therapeutic approach for acute lung injury.
Successful Ziprasidone Monotherapy in a Case of Delusional Parasitosis: A One-Year Followup
Authors: De Berardis Domenico , Serroni Nicola , Marini Stefano , Rapini Gabriella , Valchera Alessandro , Fornaro Michele , Mazza Monica , Iasevoli Felice , Martinotti Giovanni , Di Giannantonio Massimo
Published: May 2013

Delusional parasitosis is characterized by the false idea that own body is infested by invisible mites, insects, or other parasites. This case report describes a 24-year-old woman with delusional parasitosis who was treated with ziprasidone monotherapy (120 mg/day) with a complete remission of delusion and followed for one year without symptom recurrences. These findings, although preliminary, indicate that further investigation of ziprasidone monotherapy for the treatment of delusional parasitosis is warranted in further trials.
Overview of Systematic Reviews: Yoga as a Therapeutic Intervention for Adults with Acute and Chronic Health Conditions
Authors: McCall Marcy C. , Ward Alison , Roberts Nia W. , Heneghan Carl
Published: May 2013

Objectives. Overview the quality, direction, and characteristics of yoga interventions for treatment of acute and chronic health conditions in adult populations.Methods. We searched for systematic reviews in 10 online databases, bibliographic references, and hand-searches in yoga-related journals. Included reviews satisfy Oxman criteria and specify yoga as a primary intervention in one or more randomized controlled trials for treatment in adults. The AMSTAR tool and GRADE approach evaluated the methodological quality of reviews and quality of evidence.Results. We identified 2202 titles, of which 41 full-text articles were assessed for eligibility and 26 systematic reviews satisfied inclusion criteria. Thirteen systematic reviews include quantitative data and six papers include meta-analysis. The quality of evidence is generally low. Sixteen different types of health conditions are included. Eleven reviews show tendency towards positive effects of yoga intervention, 15 reviews report unclear results, and no, reviews report adverse effects of yoga. Yoga appears most effective for reducing symptoms in anxiety, depression, and pain.Conclusion. Although the quality of systematic reviews is high, the quality of supporting evidence is low. Significant heterogeneity and variability in reporting interventions by type of yoga, settings, and population characteristics limit the generalizability of results.
The Equivalence Postulate of Quantum Mechanics, Dark Energy, and the Intrinsic Curvature of Elementary Particles
Authors: Faraggi Alon E.
Published: May 2013

The equivalence postulate of quantum mechanics offers an axiomatic approach to quantum field theories and quantum gravity. The equivalence hypothesis can be viewed as adaptation of the classical Hamilton-Jacobi formalism to quantum mechanics. The construction reveals two key identities that underlie the formalism in Euclidean or Minkowski spaces. The first is a cocycle condition, which is invariant underD-dimensional Möbius transformations with Euclidean or Minkowski metrics. The second is a quadratic identity which is a representation of theD-dimensional quantum Hamilton-Jacobi equation. In this approach, the solutions of the associated Schrödinger equation are used to solve the nonlinear quantum Hamilton-Jacobi equation. A basic property of the construction is that the two solutions of the corresponding Schrödinger equation must be retained. The quantum potential, which arises in the formalism, can be interpreted as a curvature term. The author proposes that the quantum potential, which is always nontrivial and is an intrinsic energy term characterising a particle, can be interpreted as dark energy. Numerical estimates of its magnitude show that it is extremely suppressed. In the multiparticle case the quantum potential, as well as the mass, is cumulative.
X-Ray Cross-Correlation Analysis of Disordered Ensembles of Particles: Potentials and Limitations
Authors: Kurta R. P. , Altarelli M. , Vartanyants I. A.
Published: May 2013

Angular X-ray cross-correlation analysis (XCCA) is an approach to study the structure of disordered systems using the results of X-ray scattering experiments. In this paper we summarize recent theoretical developments related to the Fourier analysis of the cross-correlation functions. Results of our simulations demonstrate the application of XCCA to two- and three-dimensional (2D and 3D) disordered ensembles of particles. We show that the structure of a single particle can be recovered using X-ray data collected from a 2D disordered system of identical particles. We also demonstrate that valuable structural information about the local structure of 3D systems, inaccessible from a standard small-angle X-ray scattering experiment, can be resolved using XCCA.
Serological Evidence of Brucellosis in Goats in Kaduna North Senatorial District of Kaduna State, Nigeria
Authors: Kaltungo B. Y. , Saidu S. N. A. , Sackey A. K. B. , Kazeem H. M.
Published: May 2013

A cross-sectional study was carried out to determine the current status of Brucella antibodies in goats in Kaduna North Senatorial District of Kaduna State, Nigeria. A total of 442 serum samples (31 bucks and 411 does) were screened using Rose Bengal plate test (RBPT), serum agglutination test with ethylene diaminetetraacetic acid (SAT-EDTA), and lateral flow assay (LFA). Results. The prevalence of Brucella antibodies was found to be 25.8%, 11.1%, and 2.5% using RBPT, SAT-EDTA, and LFA, respectively. The prevalence in bucks was 32.3%, 3.2%, and 0.0% and 17.5%, 12.4%, and 3.9% in does using RBPT, SAT-EDTA, and LFA, respectively. The prevalence rates for goats less than one year of age using the tests were 1.5%, 0.0%, and 0.0%. While for those within the age bracket of one to three years, the rates were 19.4%, 10.5%, and 3.5%, respectively. The corresponding values for goats above 3 years of age were 34.2%, 15.2%, and 1.8%, respectively. The prevalence of brucellosis in goats in the study area is high which poses a threat to the development of the livestock industry and is of important zoonotic implications in Nigeria.
Cholesterol Induces Uneven Curvature of Asymmetric Lipid Bilayers
Authors: Yesylevskyy S. O. , Demchenko A. P. , Kraszewski S. , Ramseyer C.
Published: May 2013

A remarkable flexibility is observed in biological membranes, which allows them to form the structures of different curvatures. We addressed the question of intrinsic ability of phospholipid membranes to form highly curved structures and the role of cholesterol in this process. The distribution of cholesterol in the highly curved asymmetric DOPC/DOPS lipid bilayer was investigated by the coarse‐grained molecular dynamics simulations in the membrane patches with large aspect ratio. It is shown that cholesterol induces uneven membrane curvature promoting the formation of extended flattened regions of the membrane interleaved by sharp bends. It is shown that the affinity of cholesterol to anionic DOPS or neutral DOPC lipids is curvature dependent. The cholesterol prefers DOPS to DOPC in either planar or highly curved parts of the membrane. In contrast, in the narrow interval of moderate membrane curvatures this preference is inverted. Our data suggest that there is a complex self‐consistent interplay between the membrane curvature and cholesterol distribution in the asymmetric lipid bilayers. The suggested new function of cholesterol may have a biological relevance.
New Generalization of -Best Simultaneous Approximation in Topological Vector Spaces
Authors: Rawashdeh Mahmoud , Khalil Sarah
Published: May 2013

Let be a nonempty subset of a Hausdorff topological vector space , and let be a real-valued continuous function on . If for each , there exists such that , then is called -simultaneously proximal and is called -best simultaneous approximation for in . In this paper, we study the problem of -simultaneous approximation for a vector subspace in . Some other results regarding -simultaneous approximation in quotient space are presented.
Poly-γ-Glutamic Acid Attenuates Angiogenesis and Inflammation in Experimental Colitis
Authors: Davaatseren Munkhtugs , Hwang Jin-Taek , Park Jae Ho , Kim Myung-Sunny , Wang Shuaiyu , Sung Mi Jeong
Published: May 2013

Poly-γ-glutamic acid (γ-PGA), naturally secreted from various strains ofBacillus, has anti-inflammatory activity. In inflammatory bowel disease (IBD), inflammation is promoted and sustained by angiogenesis; however, the role played byγ-PGA in this condition is unclear. Therefore, we evaluatedγ-PGA effects on angiogenesis and inflammation in a dextran sulfate sodium- (DSS-) induced mouse colitis model. Experimental colitis was induced in male C57BL/6 mice by administering 3% DSS. Disease activity index (DAI), histopathological scores, microvascular density, myeloperoxidase activity, and VEGF-A and VEGFR2 expression were compared among control mice, DSS-treated mice, and mice receiving 3% DSS along withγ-PGA at 50 mg/kg body weight per day or 3% DSS withγ-PGA at 200 mg/kg body weight per day. We found thatγ-PGA significantly attenuated weight loss, DAI, and colon shortening.γ-PGA also significantly reduced histopathological evidence of injury. Moreover,γ-PGA significantly attenuated DSS-induced blood vessel densities. Furthermore,γ-PGA attenuated DSS-induced expression of VEGF-A and its receptor, VEGFR2. In addition,γ-PGA treatment led to reduced recruitment of leukocytes to the inflamed colon. Therefore, our results indicate thatγ-PGA has potential application in conditions marked by inflammatory-driven angiogenesis and mucosal inflammation.
Cancer Risk in Patients with Manifest Vascular Disease: Effects of Smoking, Obesity, and Metabolic Syndrome
Authors: van Kruijsdijk Rob C.M. , van der Graaf Yolanda , Peeters Petra H.M. , Visseren Frank L.J. ,   on behalf of the Second Manifestations of ARTerial disease (SMART) study group
Published: May 2013

Background: Patients with vascular disease may be at increased risk of cancer because of shared risk factors and common pathogenesis.

Methods: Patients with vascular disease (n = 6,172) were prospectively followed for cancer incidence. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence of the study population with that of the general population. Multivariable-adjusted hazard ratio's (HRs) of cancer were estimated for smoking status, pack-years, body mass index, waist circumference and visceral adipose tissue (VAT), and metabolic syndrome (MetS).

Results: During a median follow-up of 5.5 years, 563 patients were diagnosed with cancer. Patients with vascular disease were at increased risk of cancer [SIR = 1.19; 95% confidence interval (CI), 1.10–1.29]. Specifically, risk of lung cancer (SIR = 1.56; 95% CI, 1.31–1.83), as well as bladder cancer (SIR = 1.60; 95% CI, 1.11–2.24) and cancer of the lip, oral cavity, or pharynx in men (SIR = 1.51; 95% CI, 0.89–2.39), and colorectal (SIR = 1.71; 95% CI, 1.11–2.53) and kidney cancer (SIR = 2.92; 95% CI, 1.05–6.38) in women was increased. A relation between smoking and cancer risk was observed (HR for current smokers = 1.37; 95% CI, 1.05–1.73), whereas an increase in VAT was associated with higher breast cancer risk in women (HR = 1.42; 95% CI, 1.03–1.96). No relation between MetS and cancer risk was found.

Conclusions: Patients with vascular disease have a 19% higher cancer risk compared to the general population. Smoking increased cancer risk and abdominal obesity is a risk factor for breast cancer in female patients with vascular disease.

Impact: These results call for awareness of the increased cancer risk in patients with vascular disease among physicians and underline the necessity of lifestyle improvement not only for reducing cardiovascular risk. Cancer Epidemiol Biomarkers Prev; 22(7); 1267–77. ©2013 AACR.
Physical Activity and Risk of Lymphoma: A Meta-Analysis
Authors: Vermaete Nele V.H. , Wolter Pascal , Verhoef Gregor E.G. , Kollen Boudewijn J. , Kwakkel Gert , Schepers Leen , Gosselink Rik
Published: May 2013

Background: Physical activity has a protective effect on some types of cancer. The aim of the present meta-analysis was to explore the literature on the association between physical activity and risk of lymphoma.

Methods: A meta-analysis was conducted for cohort and case–control studies examining the association between self-reported physical activity and risk of lymphoma. Depending on statistical heterogeneity, a random or fixed effects model was used to estimate the summary OR and corresponding 95% confidence interval (CI).

Results: Seven case–control studies and 5 cohort studies were included. When data from both study designs were combined, no significant influence of physical activity on risk of lymphoma was found (pooled OR = 0.90; 95% CI: 0.79–1.02; P = 0.10). Subgroup analysis revealed a significant protective influence of physical activity on risk of lymphoma in case–control studies (pooled OR = 0.81; 95% CI: 0.68–0.96; P = 0.02). In contrast, cohort studies, which have a higher level of evidence than case–control studies, confirm the results of the primary meta-analysis (pooled OR = 1.02; 95% CI: 0.88–1.19; P = 0.76). A subsequent subgroup analysis found no significant differences between results for Hodgkin lymphoma and non-Hodgkin lymphoma (χ2 = 0.16; P = 0.69), nor between results for recreational and occupational activities (χ2 = 1.01; P = 0.31).

Conclusions: Epidemiologic research indicates no significant influence of physical activity on risk of lymphoma.

Impact: Future research should examine the association between sedentary behavior and risk of lymphoma and investigate the dose–response and timing effect of physical activity on risk of lymphoma. Cancer Epidemiol Biomarkers Prev; 22(7); 1173–84. ©2013 AACR.
C-Reactive Protein, Lipid-soluble Micronutrients, and Survival in Colorectal Cancer Patients
Authors: Cooney Robert V. , Chai Weiwen , Franke Adrian A. , Wilkens Lynne R. , Kolonel Laurence N. , Le Marchand Loïc
Published: May 2013

Background: Identification of biomarkers associated with survival in patients with cancer is important for elucidating the underlying mechanisms of cancer progression and identifying possible interventions to reduce cancer morbidity and mortality.

Methods: Using stored patient plasma samples from a multiethnic population-based case–control study of invasive colorectal cancer, we measured posttreatment blood levels of C-reactive protein (CRP) and lipid-soluble micronutrients. Patients (n = 368) were followed after phlebotomy (mean of 8 years), during which time 47% died (25% colorectal cancer specific). HRs were estimated by Cox proportional hazards regression with adjustment for stage, age at diagnosis, ethnicity, sex, smoking status, and month of blood draw.

Results: A positive association with overall risk of death was observed for CRP [HR for highest vs. lowest quintile: 1.80; 95% confidence interval (CI), 1.07–3.04; Ptrend = 0.01], whereas inverse associations were generally observed for retinol and carotenoids (HRs for overall risk of death for the highest quintile ranging from 0.5–0.8); these associations were significant for retinol (Ptrend = 0.0002), α-carotene (Ptrend = 0.02), and total carotenoids (Ptrend = 0.02) and were generally consistent across subgroups (sex, ethnicity, cancer anatomical subtype, and stage). HRs for retinol and carotenoids were attenuated somewhat after adjustment for CRP. Similar trends for CRP were observed for colorectal cancer-specific deaths (HR for highest vs. lowest tertile: 2.06; 95% CI, 1.18–3.61; Ptrend = 0.01) as for deaths from all other causes (Pheterogeneity = 0.78).

Conclusions: These observations are consistent with a direct relationship between circulating CRP and overall survival among patients with colorectal cancer.

Impact: These results, if reproduced, suggest that reduction of inflammation should be explored as a potential complementary treatment strategy. Cancer Epidemiol Biomarkers Prev; 22(7); 1278–88. ©2013 AACR.
The Clinical and Economic Burden of a Sustained Increase in Thyroid Cancer Incidence
Authors: Aschebrook-Kilfoy Briseis , Schechter Rebecca B. , Shih Ya-Chen Tina , Kaplan Edwin L. , Chiu Brian C.-H. , Angelos Peter , Grogan Raymon H.
Published: May 2013

Background: Thyroid cancer incidence is increasing worldwide at an alarming rate, yet little is known of the impact this increase will have on society. We sought to determine the clinical and economic burden of a sustained increase in thyroid cancer incidence in the United States and to understand how these burdens correlate with the National Cancer Institute's (NCI) prioritization of thyroid cancer research funding.

Methods: We used the NCI's SEER 13 database (1992–2009) and Joinpoint regression software to identify the current clinical burden of thyroid cancer and to project future incidence through 2019. We combined Medicare reimbursement rates with American Thyroid Association guidelines, and our clinical practice to create an economic model of thyroid cancer. We obtained research-funding data from the NCI's Office of Budget and Finance.

Results; By 2019, papillary thyroid cancer will double in incidence and become the third most common cancer in women of all ages at a cost of $18 to $21 billion dollars in the United States. Despite these substantial clinical and economic burdens, thyroid cancer research remains significantly underfunded by comparison, and in 2009 received only $14.7 million (ranked 30th) from the NCI.

Conclusion: The impact of thyroid cancer on society has been significantly underappreciated, as is evidenced by its low priority in national research funding levels.

Impact: Increased awareness in the medical community and the general public of the societal burden of thyroid cancer, and substantial increases in research on thyroid cancer etiology, prevention, and treatment are needed to offset these growing concerns. Cancer Epidemiol Biomarkers Prev; 22(7); 1252–9. ©2013 AACR.
Extradural Hematoma in Children: Case Series of 33 Patients
Authors: Hardtke Teichert Juliana , Rosales Jr. Paulo Renato , Blanco Lopes Policarpo , Valency Enéas Lucinara , Sica da Rocha Taís
Published: May 2013

Background: Conservative management of extradural hematomas (EDH) is relatively recent in the literature and there are few papers reporting on the pediatric population. Objective: We conduct a 20-month assessment of the treatment administered for EDH at a pediatric intensive care unit (PICU). Methods: A retrospective case series in the period described above. The main variables studied were the weight and age of the patients, the Pediatric Trauma Score, the mechanism of injury, clinical features, CT findings and the Glasgow Coma Scale score on arrival, and after 12 and 24 h. Also analyzed was whether during primary care either surgical intervention or initial conservative management was recommended. Results: In the 20 months analyzed, 33 EDH patients were admitted to the PICU. Patients had a mean age of 7.42 ± 4.66 years, mean weight of 31.16 ± 16.16 kg and mean Pediatric Trauma Scores of 7.03 ± 3.71. Out of the total sample, surgery was indicated in 12 patients (36.4%) in primary care and 21 patients (63.6%) were treated with initial conservative management. Most of the patients who were given conservative treatment had a Glasgow Coma Scale score of 15 on arrival and maintained this level throughout the hospital stay. The most prevalent sites of the hematomas were the temporal and parietal regions and the most common associated injury was skull fracture. Conclusion: In this case series, conservative treatment of EDH was most frequent; however, which factors are involved in this decision has to be better studied.
Expression of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor 1 Receptor is Associated with the Favorable Clinicopathologic Parameters in Small Intestinal Carcinomas
Authors: Shin Hyung Chan , Bae Young Kyung , Gu Mi Jin , Jung Eun Sun , Oh Young-Ha ,   The Korean Small Intestinal Cancer Study Group
Published: May 2013

Objective: The insulin-like growth factor (IGF) system has been known to play a critical role in tumor development and progression in many human cancers. However, the role of the IGF system in small intestinal carcinoma (SIC) has not been studied yet. Methods: We evaluated the expression of IGF1 and IGF1 receptor (IFG1R) in a total of 194 cases of SIC. Results: IGF1 expression was associated with well/moderate differentiation, better survival, lower pT, lower stage and no lymph node metastasis. IGF1R was more diffusely and strongly expressed in tumors with lower pT and lower stage. Conclusions: IGF1 and IGF1R expression is associated with favorable clinicopathologic parameters and may involve early carcinogenesis of SICs. Target therapy for the IGF1R signaling pathway may not have a major therapeutic role in treating SIC.
A Common APOE Polymorphism Is an Independent Risk Factor for Reduced Glomerular Filtration Rate in the Spanish RENASTUR Cohort
Authors: Coto Eliecer , Gómez Juan , Tavira Beatriz , Tranche Salvador , Ortega Francisco , Rodríguez María I. , Sánchez Emilio , Marín Rafael , Corao Ana I. , Arenas Jorge , Alvarez Victoria
Published: May 2013

Objective:APOE gene variants may contribute to the risk of chronic kidney disease. Our aim was to determine whether the common APOE-ε2/ε3/ε4 polymorphism is associated with a reduced estimated glomerular filtration rate (eGFR) in the RENASTUR population, a cohort of elderly individuals from the region Asturias (northern Spain). Methods: A total of 743 Spanish Caucasians aged 55-85 years were genotyped for the APOE-ε2/ε3/ε4 polymorphism. Individuals with a previous diagnosis of renal disease were not eligible for the study. Participants with a documented history of type 2 diabetes mellitus (T2DM) or hypertension or who were receiving antidiabetic or antihypertensive drugs were classified as diabetics and hypertensives. The eGFR was calculated using the Modification of Diet in Renal Disease formula, and those with an eGFR <60 ml/min/1.73 m2 (n = 91) were considered as having impaired renal function. The effect of alleles and genotypes on clinical (hypertension, T2DM) and analytical findings was statistically determined. Results: In addition to age and T2DM, APOE-ε2 was significantly associated with an eGFR <60 ml/min/1.73 m2 (p = 0.002; OR = 2.30). This association remained statistically significant after correction for multiple variables. Although the effect of the APOE-ε2 allele on the eGFR was observed both among diabetics and nondiabetics, the significance was stronger in the T2DM group. Conclusion: The APOE-ε2 allele is a genetic risk factor for impaired renal function among healthy elderly Spanish individuals.
Combined and independent impact of diabetes mellitus and chronic kidney disease on residual platelet reactivity
Authors: Baber Usman , Bander Jeffrey , Karajgikar Rucha , Yadav Kapil , Hadi Ali , Theodoropolous Kleanthis , Gukathasan Nilusha , Roy Swathi , Sayeneni Swapna , Scott Stuart , Kovacic Jason , Yu Jennifer , Sartori Samantha , Mehran Roxana , Uribarri Jaime , Badimon Juan , Muntner Paul , Moreno Pedro , Kini Annapoorna , Sharma Samin
Published: May 2013

Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4–6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 – 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.
Haemarthrosis stimulates the synovial fibrinolytic system in haemophilic mice
Authors: Roosendaal Goris , Coeleveld Katja , Lubberts Erik , Biesma Douwe , Lafeber Floris , Schutgens Roger , Nieuwenhuizen Laurens
Published: May 2013

Recurrent joint bleeding is the most common manifestation of haemophilia resulting in haemophilic arthropathy (HA). The exact pathophysiology is unknown, but it is suggested that arthropathy is stimulated by liberation of fibrinolytic activators from the synovium during haemarthrosis. The aim of this study was to test the hypothesis that haemarthrosis activates the local synovial fibrinolytic system in a murine haemophilia model. The right knees of haemophilic and control mice were punctured to induce haemarthrosis. The left knees served as internal control joints. Synovial levels of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), plasmin, and alpha-2-antiplasmin (A2AP) were compared between the punctured and control knees. In haemophilic mice, an increase in synovial cells expressing urokinase-type plasminogen activator (uPA) in the right punctured knee versus the left unaffected knee was observed: (47% vs 43%) (p=0.03). Additionally, in haemophilic mice, haemar-throsis induced an increase in uPA (0.016 ng/ml vs 0.01 ng/ml) (p=0.03) and plasmin (0.53 μg/ml vs 0.46 μg/ml) (p=0.01) as promoters of fibrinolysis. Synovial levels of PAI-1 (0.32 ng/ml vs 0.17 ng/ ml) (p<0.01) was also increased, whereas synovial levels of A2AP were unchanged: (0.021 μg/ml vs 0.021 μg/ml) (p=0.15). Enhanced uPA production was confirmed in human stimulated synovial fibroblast cultures and elevated levels of plasmin were confirmed harmful to human cartilage tissue explants. In this study we demonstrate that haemarthrosis in haemophilic mice induces synovial uPA expression and results in an increase in synovial plasmin levels, making the joint more vulnerable to prolonged and subsequent bleedings, and adding directly to cartilage damage.
High incidence of venous thromboembolism despite electronic alerts for thromboprophylaxis in hospitalised cancer patients
Authors: Marqués Margarita , Panizo Elena , Alfonso Ana , García-Mouriz Alberto , Gil-Bazo Ignacio , Hermida José , Schulman Sam , Páramo José , Lecumberri Ramón
Published: May 2013

Many cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VTE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical patients, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However, while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15–0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42–1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45–2.73). Interestingly, 60% of VTE episodes in cancer patients during recent years developed despite appropriate prophylaxis. Contrary to the impact on hospitalised patients without cancer, implementation of e-alerts for VTE risk did not prevent VTE effectively among those with malignancies.
Incorporation of the factor IX Padua mutation into FIX-Triple improves clotting activity in vitro and in vivo
Authors: Kao Chung-Yang , Yang Shu-Jhu , Tao Mi-Hua , Jeng Yung-Ming , Yu I-Shing , Lin Shu-Wha
Published: May 2013

Using gain-of-function factor IX (FIX) for replacement therapy for haemophilia B (HB) is an attractive strategy. We previously reported a high-activity FIX, FIX-Triple (FIX-V86A/E277A/R338A) as a good substitute for FIX-WT (wild-type) in protein replacement therapy, gene therapy, and cell therapy. Here we generated a new recombinant FIXTripleL (FIX-V86A/E277A/R338L) by replacing the alanine at residue 338 of FIX-Triple with leucine as in FIX-Padua (FIX-R338L). Purified FIX-TripleL exhibited 22-fold higher specific clotting activity and 15-fold increased binding affinity to activated FVIII compared to FIXWT. FIX-TripleL increased the therapeutic potential of FIX-Triple by nearly 100% as demonstrated with calibrated automated thrombogram and thromboelastography. FIX-TripleL demonstrated a normal clearance rate in HB mice. The clotting activity of FIX-TripleL was consistently 2- to 3-fold higher in these mice than that of FIX-Triple or FIXR338L. Gene delivery of adeno-associated virus (AAV) in HB mice showed that FIX-TripleL had 15-fold higher specific clotting activity than FIX-WT, and this activity was significantly better than FIX-Triple (10-fold) or FIX-R338L (6-fold). At a lower viral dose, FIX-TripleL improved FIX activity from sub-therapeutic to therapeutic levels. Under physiological conditions, no signs of adverse thrombotic events were observed in long-term AAV-FIX-treated C57Bl/6 mice. Hepatocellular adenomas were observed in the high- but not the medium- or the lowdose AAV-treated mice expressing FIX-WT or FIX-Triple, indicating the advantages of using hyperfunctional FIX variants to reduce viral doses while maintaining therapeutic clotting activity. Thus, incorporation of the FIX Padua mutation significantly improves the clotting function of FIX-Triple so as to optimise protein replacement therapy and gene therapy.
Role of plasma kallikrein in diabetes and metabolism
Authors: Zhou Qunfang , Fickweiler Ward , Feener Edward P.
Published: May 2013

Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.
The missense Thr211Pro mutation in the factor X activation peptide of a bleeding patient causes molecular defect in the clotting cascade
Authors: Yang Likui , Ding Qiulan , Shen Yiping , Wang Xuefeng , Rezaie Alireza
Published: May 2013

Factor X (FX) is a vitamin K-dependent coagulation zymogen, which upon activation to factor Xa assembles into the prothrombinase complex to activate prothrombin to thrombin. FX can be activated by either factor VIIa-tissue factor or factor IXa-factor VIIIa in extrinsic and intrinsic pathways, respectively. In this study, we identified a bleeding patient with moderate FX deficiency who exhibits a clotting defect only in the intrinsic pathway. Exome sequencing revealed that the patient carries a novel homozygous missense mutation that results in substitution of Thr211 with Pro in the activation peptide of FX. Thr211 is the site of an O-linked glycosylation in the activation peptide of FX. We postulated that the lack of this post-translational modification specifically impacts the activation of FX by intrinsic Xase, thereby impairing thrombin generation in the subject. To test this hypothesis, we expressed both wild-type FX and FX containing this mutation in mammalian cells and following the purification of the zymogens to homogeneity characterized their properties in both purified and plasma-based assay systems. Analysis of the results suggests that Thr211 to Pro substitution renders the FX mutant a poor substrate for both physiological activators, however, at physiological concentration of the substrate, the clotting defect manifest itself only in the intrinsic pathway, thus explaining the bleeding phenotype for the patient carrying this mutation.