bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling energy expenditure in children and adolescents using quantile regression
Authors: Yang Yunwen , Adolph Anne L. , Puyau Maurice R. , Vohra Firoz A. , Butte Nancy F. , Zakeri Issa F.
Published: May 2013

Advanced mathematical models have the potential to capture the complex metabolic and physiological processes that result in energy expenditure (EE). Study objective is to apply quantile regression (QR) to predict EE and determine quantile-dependent variation in covariate effects in nonobese and obese children. First, QR models will be developed to predict minute-by-minute awake EE at different quantile levels based on heart rate (HR) and physical activity (PA) accelerometry counts, and child characteristics of age, sex, weight, and height. Second, the QR models will be used to evaluate the covariate effects of weight, PA, and HR across the conditional EE distribution. QR and ordinary least squares (OLS) regressions are estimated in 109 children, aged 5–18 yr. QR modeling of EE outperformed OLS regression for both nonobese and obese populations. Average prediction errors for QR compared with OLS were not only smaller at the median τ = 0.5 (18.6 vs. 21.4%), but also substantially smaller at the tails of the distribution (10.2 vs. 39.2% at τ = 0.1 and 8.7 vs. 19.8% at τ = 0.9). Covariate effects of weight, PA, and HR on EE for the nonobese and obese children differed across quantiles ( P < 0.05). The associations (linear and quadratic) between PA and HR with EE were stronger for the obese than nonobese population ( P < 0.05). In conclusion, QR provided more accurate predictions of EE compared with conventional OLS regression, especially at the tails of the distribution, and revealed substantially different covariate effects of weight, PA, and HR on EE in nonobese and obese children.
A unified survival theory of the functioning of the hypocretinergic system
Authors: Chase Michael H.
Published: May 2013

This article advances the theory that the hypocretinergic (orexinergic) system initiates, coordinates, and maintains survival behaviors and survival-related processes (i.e., the Unified Survival Theory of the Functioning of the Hypocretinergic System or “Unified Hypocretinergic Survival Theory”). A priori presumptive support for the Unified Hypocretinergic Survival Theory emanates from the fact that neurons that contain hypocretin are located in the key executive central nervous system (CNS) site, the lateral hypothalamus, that for decades has been well-documented to govern core survival behaviors such as fight, flight, and food consumption. In addition, the hypocretinergic system exhibits the requisite morphological and electrophysiological capabilities to control survival behaviors and related processes. Complementary behavioral data demonstrate that all facets of “survival” are coordinated by the hypocretinergic system and that hypocretinergic directives are not promulgated except during survival behaviors. Importantly, it has been shown that survival behaviors are selectively impacted when the hypocretinergic system is impaired or rendered nonfunctional, whereas other behaviors are relatively unaffected. The Unified Hypocretinergic Survival Theory resolves the disparate, perplexing, and often paradoxical-appearing results of previous studies; it also provides a foundation for future hypothesis-driven basic science and clinical explorations of the hypocretinergic system.
3D fascicle orientations in triceps surae
Authors: Rana Manku , Hamarneh Ghassan , Wakeling James M.
Published: May 2013

The aim of this study was to determine the three-dimensional (3D) muscle fascicle architecture in human triceps surae muscles at different contraction levels and muscle lengths. Six male subjects were tested for three contraction levels (0, 30, and 60% of maximal voluntary contraction) and four ankle angles (−15, 0, 15, and 30° of plantar flexion), and the muscles were imaged with B-mode ultrasound coupled to 3D position sensors. 3D fascicle orientations were represented in terms of pennation angle relative to the major axis of the muscle and azimuthal angle (a new architectural parameter introduced in this study representing the radial angle around the major axis). 3D orientations of the fascicles, and the sheets along which they lie, were regionalized in all the three muscles (medial and lateral gastrocnemius and the soleus) and changed significantly with contraction level and ankle angle. Changes in the azimuthal angle were of similar magnitude to the changes in pennation angle. The 3D information was used for an error analysis to determine the errors in predictions of pennation that would occur in purely two-dimensional studies. A comparison was made for assessing pennation in the same plane for different contraction levels, or for adjusting the scanning plane orientation for different contractions: there was no significant difference between the two simulated scanning conditions for the gastrocnemii; however, a significant difference of 4.5° was obtained for the soleus. Correct probe orientation is thus more critical during estimations of pennation for the soleus than the gastrocnemii due to its more complex fascicle arrangement.
Red Orange: Experimental Models and Epidemiological Evidence of Its Benefits on Human Health
Authors: Grosso Giuseppe , Galvano Fabio , Mistretta Antonio , Marventano Stefano , Nolfo Francesca , Calabrese Giorgio , Buscemi Silvio , Drago Filippo , Veronesi Umberto , Scuderi Alessandro
Published: May 2013

In recent years, there has been increasing public interest in plant antioxidants, thanks to the potential anticarcinogenic and cardioprotective actions mediated by their biochemical properties. The red (or blood) orange (Citrus sinensis(L.) Osbeck) is a pigmented sweet orange variety typical of eastern Sicily (southern Italy), California, and Spain. In this paper, we discuss the main health-related properties of the red orange that include anticancer, anti-inflammatory, and cardiovascular protection activities. Moreover, the effects on health of its main constituents (namely, flavonoids, carotenoids, ascorbic acid, hydroxycinnamic acids, and anthocyanins) are described. The red orange juice demonstrates an important antioxidant activity by modulating many antioxidant enzyme systems that efficiently counteract the oxidative damage which may play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes, and cancer. The beneficial effects of this fruit may be mediated by the synergic effects of its compounds. Thus, the supply of natural antioxidant compounds through a balanced diet rich in red oranges might provide protection against oxidative damage under differing conditions and could be more effective than, the supplementation of an individual antioxidant.
Rabies in a Vaccinated 9-Month-Old German Shepherd Dog, Akure, 2010: A Case Report
Authors: Qasim A. M. , Obadua A. A. , Okewole P. A. , Tekki I. S. , Omoleye O. S.
Published: May 2013

After the onset of symptoms, the clinical course of rabies is almost invariably fatal. Rabies has traditionally been associated with dogs more than any other animal, and in parts of the world where domestic animal control and vaccination programs are limited, dogs remain the most important reservoir of the disease. We report a case of canine rabies in a vaccinated 9-month-old German shepherd female dog. The presenting clinical sign was jaw muscle paralysis with a hanging bronze color like tongue without salivation. Following encephalectomy, a rabies positive diagnosis was confirmed by fluorescent antibody technique at the Rabies Laboratory, National Veterinary Research Institute, Vom. The epidemiology of the rabies case is not understood. This case is of public health significance because of the at-risk population including animal health care service provider and animals. The following were recommended, (a) a reinvigorated control measure that includes the awareness program on prevention, responsible dog ownership with dog registration at veterinary hospitals, and registered veterinary clinics by the government and (b) a yearly rabies vaccination campaign that must be improved through the veterinary public health and other health departments collaborating.
Implementation of Control System for Hydrokinetic Energy Converter
Authors: Yuen Katarina , Apelfröjd Senad , Leijon Mats
Published: May 2013

At Uppsala University, a research group is investigating a system for converting the power in freely flowing water using a vertical-axis turbine directly connected to a permanent magnet generator. An experimental setup comprising a turbine, a generator, and a control system has been constructed and will be deployed in the Dalälven river in the town of Söderfors in Sweden. The design, construction, simulations, and laboratory tests of the control system are presented in this paper. The control system includes a startup sequence for the turbine and load control. These functions have performed satisfactorily in laboratory tests. Simulations of the system show that the power output is not maximized at the same tip-speed ratio as that which maximizes the turbine power capture.
Human Polyomavirus Reactivation: Disease Pathogenesis and Treatment Approaches
Authors: De Gascun Cillian F. , Carr Michael J.
Published: May 2013

JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of thePolyomaviridaefamily that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host.
Hepatic Steatosis, Carbohydrate Intake, and Food Quotient in Patients with NAFLD
Authors: Gonzalez Concepcion , de Ledinghen Victor , Vergniol Julien , Foucher Juliette , Le Bail Brigitte , Carlier Sabrina , Maury Elisa , Gin Henri , Rigalleau Vincent
Published: May 2013

Is steatosis related to the spontaneous carbohydrate intake in patients with NAFLD? We performed dietary records for 24 patients with NAFLD, 3 months after their liver biopsy was performed and before the deliverance of a dietary advice. The food quotient, indicator of the proportion of calories from carbohydrates, was calculated as (1.00×%  calories from carbohydrates/100) + (0.70×%  calories from lipids/100) + (0.81×%  calories from proteins/100). The associations between diet variables and steatosis% on the hepatic biopsies were tested by regression analysis, and diet variables were compared according to the presence of fibrosis. The subjects displayed a large range of steatosis, 50.5% ± 25.5 [10–90], correlated with their energy intake (1993 ± 597 kcal/d, , ) and food quotient (0.85 ± 0.02, , ), which remained significant with both variables by a multivariate regression analysis (, ). For the 17/24 patients with a hepatic fibrosis, the energy intake was lower (fibrosis: 1863 ± 503 versus others: 2382 ± 733 kcal/d, ), and their food quotients did not differ from patients without fibrosis. Hepatic steatosis was related to the energy and carbohydrate intakes in our patients; the role of dietary carbohydrates was detectable in the range of usual carbohydrate intake: 32% to 58% calories.
Experimental Study and Modeling of Fouling in Immersed Membrane Bioreactor Operating in Constant Pressure Filtration
Authors: Hosseinzadeh Mostafa , Mehrnia Mohammad Reza , Mostoufi Navid
Published: May 2013

A new mathematical model is proposed based on filtration mechanisms for the prediction of fouling in airlift immersed membrane bioreactors (iMBRs). The cake formation on the membrane surface through constant pressure filtration process in the iMBR was explained by a proposed cake filtration mechanism which assumes that no particle enters the pores when forming the cake layer on the membrane surface. The cake porosity reduction due to diffusion of particles was described by an intermediate blocking mechanism. Experimental study of fouling was also performed in a lab-scale airlift flat-sheet iMBR operating at constant vacuum. The mixed liquor suspended solid (MLSS) concentration was changed within the range of 5000 to 15000 mg/L, while the superficial air velocity was varied between 32 and 128 m3/m2/h. The presented model includes two parameters, that is, ultimate filtration resistance and initial rate of cake formation. The effect of the MLSS concentration and superficial air velocity on the parameters of the proposed model was studied. The results obtained from the model demonstrated that the ultimate filtration resistance and the initial rate of cake formation are more sensitive to the aeration rate at lower superficial velocities. It was also shown that the ultimate filtration resistance has a linear relation with MLSS concentration. A good agreement exists between the results of the model and the experimental data. The proposed model also showed a better compatibility with the experimental data compared to other fouling models available in the literature.
A Fibroid or Cancer? A Rare Case of Mixed Choriocarcinoma and Epithelioid Trophoblastic Tumour
Authors: Luk Wan Yu , Friedlander Michael
Published: May 2013

Background. Gestational trophoblastic disease (GTD) is a rare complication of pregnancy which is characterised by abnormal growth of the trophoblasts at the placental site. It is categorised into benign and malignant forms, which include hydatidiform moles (HMs) and gestational trophoblastic neoplasia (GTN), respectively. A mixed choriocarcinoma (CC) and epithelioid trophoblastic tumour (ETT) is an extremely rare subgroup of GTN, which is a highly curable but aggressive form of malignancy.Case. We report a case of mixed CC and ETT in a 41-year-old patient who presented with a 2-year history of menorrhagia and fibroid uterus in the absence of previous history of molar pregnancy. She had a 12-year interval between the antecedent pregnancy and presentation. She was treated with intensive regimen of adjuvant chemotherapy, etoposide, methotrexate, and actinomycin-D with etoposide and cisplatin (EMA-EP). She has remained disease free for more than 5 years.Conclusion. This case highlights the importance of considering GTN as one of the differential diagnoses value ofβ-HCG in patients presented with menorrhagia and growing fibroids.
Energy Cost Optimization in a Water Supply System Case Study
Authors: Moreira Daniel F. , Ramos Helena M.
Published: May 2013

The majority of the life cycle costs (LCC) of a pump are related to the energy spent in pumping, with the rest being related to the purchase and maintenance of the equipment. Any optimizations in the energy efficiency of the pumps result in a considerable reduction of the total operational cost. The Fátima water supply system in Portugal was analyzed in order to minimize its operational energy costs. Different pump characteristic curves were analyzed and modeled in order to achieve the most efficient operation point. To determine the best daily pumping operational scheduling pattern, genetic algorithm (GA) optimization embedded in the modeling software was considered in contrast with a manual override (MO) approach. The main goal was to determine which pumps and what daily scheduling allowed the best economical solution. At the end of the analysis it was possible to reduce the original daily energy costs by 43.7%. This was achieved by introducing more appropriate pumps and by intelligent programming of their operation. Given the heuristic nature of GAs, different approaches were employed and the most common errors were pinpointed, whereby this investigation can be used as a reference for similar future developments.
Healing Pathways: A Program for Women with Physical Disabilities and Depression
Authors: Hassouneh Dena , Nguyen Thuan , Chen Zunqiu , McNeff Elizabeth
Published: May 2013

Objective. The objective of this study was to test the efficacy of the Healing Pathways (HP) program in reducing clinically significantly depressive symptoms in women with physical disabilities (WPD). Healing Pathways is a peer-implemented group mental health treatment program targeting WPD who have clinically significant cooccurring depressive symptoms.Participants. Eighty women were randomized in this trial.Design. This study used a community-based participatory intervention research design. Using community-based recruiting methods, participants were recruited from Centers for Independent Living, local disability service organizations, via Craig's list as well as other community locations such as grocery stores and bus stops. Women participated in the HP program for 14 weeks.Results. The primary outcome variable for this study was reduction in depressive symptoms as measured by the Center for Epidemiologic Depression Scale (CES-D). We found that there was a significant interaction effect of treatment by time on depression scores,F(3,210) = 9.51,P<0.0001, partialη2=0.101. Investigation of the predicted mean profile over time in the intervention group demonstrated that depression scores decreased greatly from baseline to the first posttest and remained stable in the two followups, whereas there was a little change in the mean profile over time in the control group.Conclusion. The HP program has demonstrated initial efficacy in reducing depressive symptoms in women with physical disabilities.
Multifocal Retroperitoneal Sarcoma
Authors: Theodosopoulos Theodosios , Dellaportas Dionysios , Psychogiou Vasiliki , Yiallourou Anneza , Polymeneas George , Gkiokas Georgios , Voros Dionysios
Published: May 2013

Introduction. Retroperitoneal sarcomas comprise a small proportion of all soft tissue sarcomas, and multiple factors influence their clinical behavior. Histopathological type and grade as well as complete surgical resection especially on the first operative attempt are well recognized as the main prognostic factors. Multifocality is another prognostic factor, which compromises therapy and finally makes prognosis worse due to multiple adverse implications.Case Presentation. A rare case of a 65-year-old male patient suffering from a multifocal retroperitoneal liposarcoma successfully treated in our hospital is presented herein.Discussion. Also, general considerations for these tumors are discussed, and especially multifocality is underlined as an ominous sign of retroperitoneal sarcomas behavior. Despite multifocality, once again complete surgical excision remains the mainstay of treatment of these patients, as long as further systemic and local therapies do not provide durable results.
Recent Pharmacological Developments on Rhodanines and 2,4-Thiazolidinediones
Authors: Bhatti Ravinder Singh , Shah Sakshi , Suresh  , Krishan Pawan , Sandhu Jagir S.
Published: May 2013

Thiazolidines are five-member heterocyclic having sulfur, nitrogen, and oxygen atoms in their ring structure and exhibiting potent as well as wide range of pharmacological activities. In this minireview, recent updates on synthesis and pharmacological evaluations of molecules based on 2,4-thiazolidine and rhodanine are discussed.
Lumbar Ureteral Stenosis due to Endometriosis: Our Experience and Review of the Literature
Authors: Butticè Salvatore , Laganà Antonio Simone , Barresi Valeria , Inferrera Antonino , Mucciardi Giuseppe , Di Benedetto Antonina , D'Amico Carmela Emanuela , Magno Carlo
Published: May 2013

Endometriosis is a chronic gynaecological disorder characterized by the presence of endometrial tissue outside the uterus. The disease most often affects the ovaries, uterine ligaments, fallopian tubes, and cervical-vaginal region. Urinary tract involvement is rare, accounting for around 1%-2% of all cases, of which 84% are in the bladder. We report a case of isolated lumbar ureteral stenosis due to endometriosis in a 37-year-old patient. The patient came to our observation complaining from lumbar back pain and presented with severe fever. The urological examination found monolateral left positive sign of Giordano. Blood tests evidenced marked lymphocytosis and increased valued of C-reactive protein. Urologic ultrasound showed hydronephrosis of first degree in the left kidney and absence of images related to stones bilaterally. Uro-CT scan evidenced ureteral stenosis at the transition between the iliac and pelvic tracts. We addressed the patient to surgery, and performed laparoscopic excision of the paraureteral bulk, endoscopic mechanical ureteral dilation, and stenting. The histological examination evidenced glandular structures lined by simple epithelium and surrounded by stroma. Immunohistochemical test of the glandular epithelium showed positivity for estrogen and progesterone receptors and moreover stromal cells were positive for CD10. The finding suggested a very rare diagnosis of isolated lumbar ureteral endometriosis.
Multicenter Randomized Trial of 10-French versus 11.5-French Plastic Stents for Malignant Biliary Obstruction
Authors: Wagh Mihir S. , de Bellis Mario , Fogel Evan L. , Frakes James T. , Johanson John F. , Qaseem Tahir , Howell Douglas A. , Lehman Glen A. , Sherman Stuart
Published: May 2013

Background. There is little prospective data on whether bigger plastic stents are better for patients with malignant biliary obstruction with jaundice. Goals. Multicenter prospective study to compare technical success, clinical response, stent occlusion, and patient survival in patients with malignant biliary obstruction randomized to 10-French or 11.5-French plastic stent. Study. Patients with malignant biliary obstruction were randomized to 10-French or 11.5-French biliary stents. Patients were prospectively assessed for stent occlusion, stent-related interventions, hospital stay, and change in bilirubin. Main outcome measurements included technical success, clinical response, rates of stent occlusion, and survival. Results. 234 patients (47 hilar and 187 common bile duct strictures) were randomized. Outcomes were similar for the 10-French and 11.5-French groups (technical success 99.1% versus 97.4%, P=0.37). Overall, median stent survival was 213 days, but there was no statistically significant difference in stent survival between 10-French and 11.5-French stents (149 versus 258 days, P=0.16). Stent survival was significantly longer when placed for common bile duct versus hilar strictures (231 versus 115 days, P=0.049). Conclusions. The theoretical advantage of improved bile flow for the 11.5-French stent does not translate into more prolonged patency, better clinical response, and longer patient survival than the 10-French stent.
Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time?
Authors: Cucinotto Iole , Fiorillo Lucia , Gualtieri Simona , Arbitrio Mariamena , Ciliberto Domenico , Staropoli Nicoletta , Grimaldi Anna , Luce Amalia , Tassone Pierfrancesco , Caraglia Michele , Tagliaferri Pierosandro
Published: May 2013

Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms.
Providers’ Perspectives on Provision of Family Planning to HIV-Positive Individuals in HIV Care in Nyanza Province, Kenya
Authors: Newmann Sara J. , Mishra Kavita , Onono Maricianah , Bukusi Elizabeth A. , Cohen Craig R. , Gage Olivia , Odeny Rose , Schwartz Katie D. , Grossman Daniel
Published: May 2013

Objective. To inform an intervention integrating family planning into HIV care, family planning (FP) knowledge, attitudes and practices, and perspectives on integrating FP into HIV care were assessed among healthcare providers in Nyanza Province, Kenya.Methods. Thirty-one mixed-method, structured interviews were conducted among a purposive sample of healthcare workers (HCWs) from 13 government HIV care facilities in Nyanza Province. Structured questions and case scenarios assessed contraceptive knowledge, training, and FP provision experience. Open-ended questions explored perspectives on integration. Data were analyzed descriptively and qualitatively.Results. Of the 31 HCWs interviewed, 45% reported previous FP training. Few providers thought long-acting methods were safe for HIV-positive women (19% viewed depot medroxyprogesterone acetate as safe and 36% viewed implants and intrauterine contraceptives as safe); fewer felt comfortable recommending them to HIV-positive women. Overall, providers supported HIV and family planning integration, yet several potential barriers were identified including misunderstandings about contraceptive safety, gendered power differentials relating to fertility decisions, staff shortages, lack of FP training, and contraceptive shortages.Conclusions. These findings suggest the importance of considering issues such as patient flow, provider burden, commodity supply, gender and cultural issues affecting FP use, and provider training in FP/HIV when designing integrated FP/HIV services in high HIV prevalence areas.
Combination of Protein Coding and Noncoding Gene Expression as a Robust Prognostic Classifier in Stage I Lung Adenocarcinoma
Authors: Akagi Ichiro , Okayama Hirokazu , Schetter Aaron J. , Robles Ana I. , Kohno Takashi , Bowman Elise D. , Kazandjian Dickran , Welsh Judith A. , Oue Naohide , Saito Motonobu , Miyashita Masao , Uchida Eiji , Takizawa Toshihiro , Takenoshita Seiichi , Skaug Vidar , Mollerup Steen , Haugen Aage , Yokota Jun , Harris Curtis C.
Published: May 2013

Prognostic tests for patients with early-stage lung cancer may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early-stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival (RFS) were evaluated using microarray data from 148 patients with stage I lung adenocarcinoma. Seven genes associated with RFS were further examined by quantitative reverse transcription PCR in 291 lung adenocarcinoma tissues from Japan, the United States, and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publicly available lung adenocarcinoma expression profiling datasets. The results suggest that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with miRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high-risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of patients with stage I lung adenocarcinoma. Cancer Res; 73(13); 3821–32. ©2013 AACR.
Single-Nucleotide Polymorphisms in Genes Encoding for CC Chemokines were Not Associated with the Risk of Non-Hodgkin Lymphoma
Authors: Chen Qiong , Zheng Tongzhang , Lan Qing , Lerro Catherine , Zhao Nan , Qin Qin , Hu Xiaobin , Huang Huang , Liang Jiaxin , Holford Theodore , Leaderer Brian , Boyle Peter , Chanock Stephen J. , Rothman Nathaniel , Zhang Yawei
Published: May 2013

Background: Chemokines play a pivotal role in immune regulation and response, and previous studies suggest an association between immune deficiency and non-Hodgkin lymphoma (NHL).

Methods: We evaluated the association between NHL and polymorphisms in 18 genes (CCL1, CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL18, CCL20, CCL24, CCL26, CCR1, CCR3, CCR4, CCR6, CCR7, CCR8, and CCR9) encoding for the CC chemokines using data from a population-based case–control study of NHL conducted in Connecticut women.

Results:CCR8 was associated with diffuse large B-cell lymphoma (DLBCL; P = 0.012), and CCL13 was associated with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL; P = 0.003) at gene level. After adjustment for multiple comparisons, none of the genes or single-nucleotide polymorphisms (SNP) were associated with risk of overall NHL or NHL subtypes.

Conclusions: Our results suggest that the genes encoding for CC chemokines are not significantly associated with the risk of NHL, and further studies are needed to verify these findings.

Impact: Our data indicate that CC chemokine genes were not associated with NHL risk. Cancer Epidemiol Biomarkers Prev; 22(7); 1332–5. ©2013 AACR.
Phenotypic Polarization of Macrophages in Atherosclerosis
Authors: Leitinger Norbert , Schulman Ira G.
Published: May 2013

Macrophages orchestrate the inflammatory response in inflamed tissues, and recent work indicates that these cells can alter their phenotypes and functions accordingly in response to changes in the microenvironment. Initial work in models of cardiovascular disease used immunologic markers to characterize macrophage phenotypes present in atherosclerotic plaque, and these studies have lately been extended through the use of markers that are more specific for atherosclerosis and metabolic disease. Together, these studies have led to a novel view of the function of macrophages in the development of atherosclerosis that suggests dynamic plasticity. Understanding this plasticity and the ensuing macrophage heterogeneity could lead to novel strategies of pharmacological intervention to combat chronic inflammation in metabolic diseases. Most importantly, revealing the functional characteristics of individual macrophage phenotypes will lead to a better understanding of their contribution to lesion development and plaque stability.
Multiple Inflammatory Biomarkers in Relation to Cardiovascular Events and Mortality in the Community
Authors: Schnabel Renate B. , Yin Xiaoyan , Larson Martin G. , Yamamoto Jennifer F. , Fontes João D. , Kathiresan Sekar , Rong Jian , Levy Daniel , Keaney John F. , Wang Thomas J. , Murabito Joanne M. , Vasan Ramachandran S. , Benjamin Emelia J.
Published: May 2013

Objective—

Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality.

Approach and Results—

We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61±9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02–1.35; nominal
P
=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01–1.32; nominal
P
=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19–1.49;
P
<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12–1.37;
P
<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12–1.39;
P
<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (
P
<0.0001), but not for CVD.

Conclusions—

Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.
Molecular Basis of Antiangiogenic Thrombospondin-1 Type 1 Repeat Domain Interactions With CD36
Authors: Klenotic Philip A. , Page Richard C. , Li Wei , Amick Joseph , Misra Saurav , Silverstein Roy L.
Published: May 2013

Objective—

Antiangiogenic activity of thrombospondin-1 and related proteins is mediated by interactions between thrombospondin type 1 repeat (TSR) domains and the CD36, LIMP-2, Emp sequence homology (CLESH) domain of the endothelial cell receptor CD36. We sought to characterize key molecular determinants of the interaction between thrombospondin-1 TSR domains and the CD36 CLESH domain.

Approach and Results—

Recombinant thrombospondin-1 TSR2 and TSR(2,3) constructs inhibited microvascular endothelial cell migration, microvascular endothelial cell tube formation, and vessel sprouting in aortic ring assays. Interaction with CD36 CLESH decoy peptides negated these effects. Mutational analyses identified a cluster of residues that confer positive charge to the TSR2 surface and mediate interaction with CD36 CLESH. Antiangiogenic activity was significantly reduced by charge-neutralizing mutations of the Arg-Trp ladder in TSR2, but not TSR3. Additionally, I438 and K464 of TSR2 were shown to be required for CD36 CLESH binding to TSR2. A complementary acidic cluster within CD36 CLESH is also required for antiangiogenic activity.

Conclusions—

Thrombospondin-1 interacts with CD36 CLESH through electrostatic interactions mediated by a positively charged TSR2 surface and multiple negatively charged CD36 CLESH residues. Two key residues serve as specificity determinants that identify other TSR domains that interact with CD36 CLESH.
Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy
Authors: Gillard Baiba K. , Raya Joe L. , Ruiz-Esponda Raul , Iyer Dinakar , Coraza Ivonne , Balasubramanyam Ashok , Pownall Henry J.
Published: May 2013

Objective—

HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non–HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional.

Approach and Results—

Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, low-density lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[
3
H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (
P
<0.001).

Conclusions—

Compared with NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.
Overexpression of Angiopoietin-Like Protein 4 Protects Against Atherosclerosis Development
Authors: Georgiadi Anastasia , Wang Yanan , Stienstra Rinke , Tjeerdema Nathanja , Janssen Aafke , Stalenhoef Anton , van der Vliet J. Adam , de Roos Albert , Tamsma Jouke T. , Smit Johannes W.A. , Tan Nguan Soon , Müller Michael , Rensen Patrick C.N. , Kersten Sander
Published: May 2013

Objective—

Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in macrophages and examined the impact of Angptl4 on atherosclerosis development.

Approach and Results—

Macrophage activation elicited by pathogen-recognition receptor agonists decreased Angptl4 expression, whereas lipid loading by intralipid and oxidized low-density lipoprotein increased Angptl4 expression. Consistent with an antilipotoxic role of Angptl4, recombinant Angptl4 significantly decreased uptake of oxidized low-density lipoprotein by macrophages, via lipolysis-dependent and -independent mechanisms. Angptl4 protein was detectable in human atherosclerotic lesions and localized to macrophages. Transgenic overexpression of Angptl4 in atherosclerosis-prone apolipoprotein E*3-Leiden mice did not significantly alter plasma cholesterol and triglyceride levels. Nevertheless, Angptl4 overexpression reduced lesion area by 34% (
P
<0.05). In addition, Angptl4 overexpression decreased macrophage content (−41%;
P
<0.05) and numbers of monocytes adhering to the endothelium wall (−37%;
P
<0.01). Finally, plasma Angptl4 was independently and negatively associated with carotid artery sclerosis measured by 3-T MRI in subjects with metabolic syndrome and low-grade systemic inflammation.

Conclusions—

Angptl4 suppresses foam cell formation to reduce atherosclerosis development. Stimulation of Angptl4 in macrophages by oxidized low-density lipoprotein may protect against lipid overload.
Cardiovascular Risk Profile and Cognitive Function in Young, Middle-Aged, and Elderly Subjects
Authors: Joosten Hanneke , van Eersel Marlise E.A. , Gansevoort Ron T. , Bilo Henk J.G. , Slaets Joris P.J. , Izaks Gerbrand J.
Published: May 2013

Background and Purpose—

Cognitive decline occurs earlier than previously realized and is already evident at the age of 45. Because cardiovascular risk factors are established risk factors for cognitive decline in old age, we investigated whether cardiovascular risk factors are also associated with cognitive decline in young and middle-aged groups.

Methods—

The cross-sectional study included 3778 participants aged 35 to 82 years (mean age, 54 years) and free of cardiovascular disease and stroke. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; worst score, 0; best score, 12 points). Overall cardiovascular risk was assessed with the Framingham Risk Score (FRS) for general cardiovascular disease (best score, −5; worst score, 33 points).

Results—

Mean RFFT score (SD) was 70 (26) points, median VAT score (interquartile range) was 10 (9–11) points, and mean FRS (SD) was 10 (6) points. Using linear regression analysis adjusting for educational level, RFFT was negatively associated with FRS. RFFT score decreased by 1.54 points (95% confidence interval, −1.66 to −1.44;
P
<0.001) per point increase in FRS. This negative association was not only limited to older age groups, but also found in the young (35–44 years). The main influencing components of the FRS were age (
P
<0.001), diabetes mellitus (
P
=0.001), and smoking (
P
<0.001). Similar results were found for VAT score as outcome measure.

Conclusions—

In this large population–based cohort, a worse overall cardiovascular risk profile was associated with poorer cognitive function. This association was already present in young adults aged 35 to 44 years.
White-Coat and Masked Hypertension Are Associated With Carotid Atherosclerosis in a General Population
Authors: Fukuhara Masayo , Arima Hisatomi , Ninomiya Toshiharu , Hata Jun , Hirakawa Yoichiro , Doi Yasufumi , Yonemoto Koji , Mukai Naoko , Nagata Masaharu , Ikeda Fumie , Matsumura Kiyoshi , Kitazono Takanari , Kiyohara Yutaka
Published: May 2013

Background and Purpose—

On the basis of combined measurements of clinic blood pressure (CBP) and home blood pressure (HBP), blood pressure status can be divided into normotension, white-coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Despite the clear impact of MHT and SHT on clinical and subclinical arterial disease, uncertainty about the influence of WCHT remains. The objective of this study was to investigate the associations of WCHT, MHT, and SHT with carotid atherosclerosis in a general population.

Methods—

This is a cross-sectional survey of 2915 community-dwelling Japanese aged ≥40 years. Normotension was defined as CBP<140/90 and HBP<135/85 mm Hg; WCHT, CBP≥140/90 and HBP<135/85 mm Hg; MHT, CBP<140/90 and HBP≥135/85 mm Hg; and SHT, CBP≥140/90 and HBP≥135/85 mm Hg. Mean intima-media thickness of carotid arteries was measured using a computer-automated system, and carotid stenosis was defined as diameter stenosis ≥30%.

Results—

There were 1374 subjects (47.1%) with normotension, 200 (6.9%) with WCHT, 639 (21.9%) with MHT, and 702 (24.1%) with SHT. The geometric average of mean intima-media thickness was significantly higher among subjects with WCHT (0.73 mm), MHT (0.77 mm), and SHT (0.77 mm) than those with normotension (0.67 mm; all
P
<0.001 versus normotension). Compared with normotension, all types of hypertension were also associated with increased likelihood of carotid stenosis (age- and sex-adjusted odds ratio, 2.36 [95% confidence interval, 1.27–4.37] for WCHT, 1.95 [1.25–3.03] for MHT, and 3.02 [2.01–4.54] for SHT). These associations remained significant even after adjustment for other cardiovascular risk factors.

Conclusions—

WCHT, as well as MHT, and SHT were associated with carotid atherosclerosis in a general Japanese population.
CYP2C19 Polymorphisms and Antiplatelet Effects of Clopidogrel in Acute Ischemic Stroke in China
Authors: Jia Dong-mei , Chen Zhi-bin , Zhang Mei-juan , Yang Wen-jie , Jin Jia-li , Xia Yong-quan , Zhang Chun-lei , Shao Yuan , Chen Cong , Xu Yun
Published: May 2013

Background and Purpose—

Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke.

Methods—

A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated.

Results—

The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance.

Conclusions—

CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke.

Clinical Trial Registration Information—

URL:
http://www.chictr.org/
. Unique Identifier: ChiCTR-OCH-12002681.
Can Diffusion-Weighted Imaging–Fluid-Attenuated Inversion Recovery Mismatch (Positive Diffusion-Weighted Imaging/Negative Fluid-Attenuated Inversion Recovery) at 3 Tesla Identify Patients With Stroke at <4.5 Hours?
Authors: Emeriau Samuel , Serre Isabelle , Toubas Olivier , Pombourcq Francis , Oppenheim Catherine , Pierot Laurent
Published: May 2013

Background and Purpose—

At 1.5 T, diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI–FLAIR) mismatch helps identify strokes within 4.5 hours of onset. However, at 3T, studies have found divergent results. The goal of this study was to determine whether DWI–FLAIR mismatch at 3T would also be helpful for identifying patients within 4.5 hours of symptom onset.

Methods—

All patients presenting with an ischemic stroke in the middle cerebral artery territory and explored with 3T MRI within 12 hours between November 2007 and April 2012 were included in this retrospective study. Two readers analyzed the DWI and FLAIR images. Logistic regression was performed to determine independent predictors of FLAIR visibility. Also, the predictive values of a mismatch for identifying patients with stroke onset ≤4.5 hours were estimated.

Results—

The study included 194 patients. The only predictive factor of FLAIR visibility was delayed MRI acquisition. The DWI–FLAIR mismatch was able to identify patients within 4.5 hours of stroke onset with relatively low sensitivity (0.55; 95% confidence interval, 0.48–0.63), low specificity (0.60; 95% confidence interval, 0.42–0.77), high positive predictive value (0.88; 95% confidence interval, 0.82–0.94), and very low negative predictive value (0.19; 95% confidence interval, 0.11–0.28). In addition, 44.5% of patients had a positive FLAIR sequence within 4.5 hours.

Conclusions—

This study improves our understanding of DWI–FLAIR mismatch as an imaging biomarker for wake-up management of patients with stroke. At 3T, the presence of a DWI–FLAIR mismatch was able to identify stroke onset of <4.5 hours. However, 44.5% of such stroke cases demonstrated FLAIR signal changes.
The Spatial Sound Description Interchange Format: Principles, Specification, and Examples
Authors: Peters Nils , Lossius Trond , Schacher Jan C.
Published: May 2013

SpatDIF, the Spatial Sound Description Interchange Format, is an ongoing collaborative effort offering a semantic and syntactic specification for storing and transmitting spatial audio scene descriptions. The SpatDIF core is a lightweight minimal solution providing the most essential set of descriptors for spatial sound scenes. Additional descriptors are introduced as extensions, expanding the namespace and scope with respect to authoring, scene description, rendering, and reproduction of spatial sound. A general overview presents the principles informing the specification, as well as the structure and the terminology of the SpatDIF syntax. Two use cases exemplify SpatDIF's potential for pre-composed pieces as well as interactive installations, and several prototype implementations that have been developed show its real-life utility.
Surveillance and/of Nature
Authors: Haggerty Kevin D. , Trottier Daniel
Published: May 2013

Surveillance is a key aspect of contemporary industrialized Western societies. The now extensive literature on the dynamics of surveillance has, however, curiously overlooked how nonhuman phenomena have been incorporated into quite different surveillance-related agendas. This paper provides a general overview of some of the ways that such surveillance operates, pointing to some of the social and political consequences that flow from recognizing the broad dynamics of surveillance and/of nature.