bluuebunny/crossref_metadata_2025 huggingface dataset:
Death Anxiety, Reliability, Validity, and Factorial Structure of the Farsi Form of the Arabic Scale of Death Anxiety in Iranian Old-Aged Persons
Authors: Dadfar Mahboubeh , Lester David , Bahrami Fazel
Published: October 2016

The present study is aimed at examining the level of death anxiety and the sex-related differences among old-aged Iranian individuals sample to compare the old-aged persons with young college students and to explore the psychometric properties of the Arabic Scale of Death Anxiety (ASDA) factors in old-aged sample. A sample of 146 volunteer Iranian individuals took part in the study. The mean ages were 68.58 (SD = 7.10), men 68.81 (SD = 7.44) and women 68.28 (SD = 6.76), respectively. The mean score of the ASDA was 51.09 (SD = 20.19). Cronbach’s alpha of the ASDA was found to be high (0.94); and Spearman-Brown coefficient was 0.92. Women had a significantly higher mean total score on the ASDA. Old-aged individuals had a significantly higher mean ASDA total score than younger college students (M age = 25.77). The factor analysis of the ASDA items yielded three factors accounting for 67.88% of the total variance labeled (F1) fear of dead people and tombs; (F2) fear of lethal disease and postmortem events; and (F3) death fear. These factors were highly replicable with previous factors extracted from a middle-aged Kuwaiti sample. On the basis of the present results, there are the following three general conclusions: death anxiety is not significantly correlated with age; the sex-related differences on death anxiety are striking in the Iranian samples; and the ASDA has a highly replicable factor structure among two Iranian and Arab countries.
Man versus Machine: Software Training for Surgeons—An Objective Evaluation of Human and Computer-Based Training Tools for Cataract Surgical Performance
Authors: Din Nizar , Smith Phillip , Emeriewen Krisztina , Sharma Anant , Jones Simon , Wawrzynski James , Tang Hongying , Sullivan Paul , Caputo Silvestro , Saleh George M.
Published: October 2016

This study aimed to address two queries: firstly, the relationship between two cataract surgical feedback tools for training, one human and one software based, and, secondly, evaluating microscope control during phacoemulsification using the software. Videos of surgeons with varying experience were enrolled and independently scored with the validated PhacoTrack motion capture software and the Objective Structured Assessment of Cataract Surgical Skill (OSACCS) human scoring tool. Microscope centration and path length travelled were also evaluated with the PhacoTrack software. Twenty-two videos correlated PhacoTrack motion capture with OSACCS. The PhacoTrack path length, number of movements, and total procedure time were found to have high levels of Spearman’s rank correlation of -0.6792619 (p=0.001), -0.6652021 (p=0.002), and -0.771529 (p=0001), respectively, with OSACCS. Sixty-two videos evaluated microscope camera control. Novice surgeons had their camera off the pupil centre at a far greater mean distance (SD) of 6.9 (3.3) mm, compared with experts of 3.6 (1.6) mm (p≪0.05). The expert surgeons maintained good microscope camera control and limited total pupil path length travelled 2512 (1031) mm compared with novices of 4049 (2709) mm (p≪0.05). Good agreement between human and machine quantified measurements of surgical skill exists. Our results demonstrate that surrogate markers for camera control are predictors of surgical skills.
A Rare Clinical Course of Seronegative Pulmonary-Renal Syndrome
Authors: Fröhlich-Gildhoff M. , Jabs W. J. , Berhold C. , Kuhlmann M. K. , Ketterer U. , Kische S. , Ince H.
Published: October 2016

Purpose. Pulmonary-renal syndrome (PRS) is characterized by diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis mainly due to autoimmune etiologies. Seronegative PRS is a challenging entity to the clinician, since early diagnosis may be missed leading to delayed appropriate treatment.Materials and Methods. We present the clinical course of a 77-year-old patient who was admitted under the suspected diagnosis of pneumogenic sepsis and septic renal failure with fever, dyspnea, and elevated CRP levels. The diagnosis of pulmonary-renal syndrome was initially missed because of the absence of autoantibodies in all serological findings.Results.Despite delayed initiation of immunosuppressive therapy and a prolonged period of dialysis and extracorporeal membrane oxygenation the patient recovered well and was released to a rehabilitation center with nearly normalized creatinine levels. The diagnosis of PRS was established by renal biopsy.Conclusion. This case illustrates the important differential diagnosis of seronegative pulmonary-renal syndrome in patients with pulmonary and renal impairment.
Simplifying the Treatment of Bone Atrophy in the Posterior Regions: Combination of Zygomatic and Wide-Short Implants—A Case Report with 2 Years of Follow-Up
Authors: Faot Fernanda , Thomé Geninho , Bielemann Amália Machado , Hermann Caio , Melo Ana Cláudia Moreira , Padovan Luis Eduardo Marques , de Mattias Sartori Ivete Aparecida
Published: October 2016

The rehabilitation of maxillary and mandibular bone atrophy represents one of the main challenges of modern oral implantology because it requires a variety of procedures, which not only differ technically, but also differ in their results. In the face of limitations such as deficiencies in the height and thickness of the alveolar structure, prosthetic rehabilitation has sought to avoid large bone reconstruction through bone grafting; this clinical behavior has become a treatment system based on evidence from clinical scientific research. In the treatment of atrophic maxilla, the use of zygomatic implants has been safely applied as a result of extreme technical rigor and mastery of this surgical skill. For cases of posterior mandibular atrophy, short implants with a large diameter and a combination of short and long implants have been recommended to improve biomechanical resistance. These surgical alternatives have demonstrated a success rate similar to that of oral rehabilitation with the placing of conventional implants, allowing the adoption of immediate loading protocol, a decrease in morbidity, simplification and speed of the treatment, and cost reduction. This case report presents complete oral rehabilitation in a patient with bilateral bone atrophy in the posterior regions of the maxilla and mandible with the goal of developing and increasing posterior occlusal stability during immediate loading.
Early Inflammatory Response following Traumatic Brain Injury in Rabbits Using USPIO- and Gd-Enhanced MRI
Authors: Ouyang Lin , Zeng Si , Zheng Gang , Lu Guang Ming
Published: October 2016

Purpose. To monitor the inflammatory response (IR) following traumatic brain injury (TBI) before and after the rehabilitation of the blood-brain barrier (BBB) in rabbits using USPIO- and Gd-enhanced MRI. Materials and Methods. Twenty white big-eared rabbits with mild TBI (mTBI) were randomly and equally divided into four groups. Rabbits were sacrificed for the brain specimens immediately after the last MRI-monitoring. Sequences were tse-T1WI, tse-T2WI, Gd-T1WI, and USPIO-T1WI. Dynamical MRI presentations were evaluated and compared with pathological findings for each group. Results. Twenty-four hours after injury, all rabbits displayed high signal foci on T2WI, while only 55% lesions could be found on Gd-T1WI and none on USPIO-T1WI. The lesions were enhanced on Gd-T1WI in 100% subjects after 48 h and the enhancement sizes augmented to the largest after 72 h. At the time point of 72 h after TBI, 90% lesions were enhanced by USPIO. Five days after injury, 19 lesions showed decreased Gd-enhancement and one disappeared; however, USPIO-enhancement became larger than before. Pathological findings showed microglias slightly appeared in dense leukocytes at 48 h, but became the dominant inflammatory cells after five days. Conclusions. Dynamic IR following injury could be monitored by combination of Gd- and USPIO-MRI in mTBI rabbits.
Self-Dual Abelian Codes in Some Nonprincipal Ideal Group Algebras
Authors: Choosuwan Parinyawat , Jitman Somphong , Udomkavanich Patanee
Published: October 2016

The main focus of this paper is the complete enumeration of self-dual abelian codes in nonprincipal ideal group algebrasF2k[A×Z2×Z2s]with respect to both the Euclidean and Hermitian inner products, wherekandsare positive integers andAis an abelian group of odd order. Based on the well-known characterization of Euclidean and Hermitian self-dual abelian codes, we show that such enumeration can be obtained in terms of a suitable product of the number of cyclic codes, the number of Euclidean self-dual cyclic codes, and the number of Hermitian self-dual cyclic codes of length2sover some Galois extensions of the ringF2k+uF2k, whereu2=0. Subsequently, general results on the characterization and enumeration of cyclic codes and self-dual codes of lengthpsoverFpk+uFpkare given. Combining these results, the complete enumeration of self-dual abelian codes inF2k[A×Z2×Z2s]is therefore obtained.
Bilateral Simultaneous Pseudoangiomatous Stromal Hyperplasia of the Breasts and Axillae: Imaging Findings with Pathological and Clinical Correlation
Authors: Alikhassi Afsaneh , Ensani Fereshteh , Omranipour Ramesh , Abdollahi Alireza
Published: October 2016

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a pathology that is usually diagnosed by accident during pathological examination of other breast lesions. PASH is an uncommon and benign tumoral lesion of the mammary stroma that can be pathologically mistaken for other tumours, such as phyllodes, fibroadenoma, and sometimes even angiosarcoma. We report the case of a 45-year-old woman with complaints of huge bilateral breast enlargement. This is a rare case of PASH presenting with gigantomastia and involving bilateral breasts and axillae simultaneously. Mammography, ultrasonography, and MRI features are illustrated with histopathological correlation.
In Vitro TNF‐α Inhibitory Activity of Brazilian Plants and Anti‐Inflammatory Effect of Stryphnodendron adstringens in an Acute Arthritis Model
Authors: Henriques Bárbara O. , Corrêa Olívia , Azevedo Elaine Patrícia C. , Pádua Rodrigo M. , Oliveira Vívian Louise S. de , Oliveira Thiago Henrique C. , Boff Daiane , Dias Ana Carolina F. , Souza Danielle G. de , Amaral Flávio A. , Teixeira Mauro M. , Castilho Rachel O. , Braga Fernão C.
Published: October 2016

Stryphnodendron species, popularly named “barbatimão,” are traditionally used in Brazil as anti‐inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor‐alpha (TNF‐α) in lipopolysaccharide‐ (LPS‐) stimulated THP‐1 cells, as well as their anti‐arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration‐dependent inhibition of TNF‐α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose‐dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI‐MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B‐type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti‐inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity.
CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α
Authors: Tian Xi , Nguyen Minh , Foote Henry P. , Caster Joseph M. , Roche Kyle C. , Peters Christian G. , Wu Pauline , Jayaraman Lata , Garmey Edward G. , Tepper Joel E. , Eliasof Scott , Wang Andrew Z.
Published: October 2016

Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle–drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared with standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demonstrated that the addition of CRLX101 to standard chemoradiotherapy significantly increased therapeutic efficacy by inhibiting DNA repair and HIF1α pathway activation in tumor cells. Notably, CRLX101 was more effective than oxaliplatin at enhancing the efficacy of chemoradiotherapy, with CRLX101 and 5-fluorouracil producing the highest therapeutic efficacy. Gastrointestinal toxicity was also significantly lower for CRLX101 compared with CPT when combined with radiotherapy. Our results offer a preclinical proof of concept for CRLX101 as a modality to improve the outcome of neoadjuvant chemoradiotherapy for rectal cancer treatment, in support of ongoing clinical evaluation of this agent (LCC1315 NCT02010567). Cancer Res; 77(1); 112–22. ©2016 AACR.
Mechanisms through Which Hypoxia-Induced Caveolin-1 Drives Tumorigenesis and Metastasis in Hepatocellular Carcinoma
Authors: Mao Xiaowen , Wong Sivia Yuen Sze , Tse Edith Yuk Ting , Ko Frankie Chi Fat , Tey Sze Keong , Yeung Yin Shan , Man Kwan , Lo Regina Cheuk-Lam , Ng Irene Oi-Lin , Yam Judy Wai Ping
Published: October 2016

In solid tumors, hypoxia triggers an aberrant vasculogenesis, enhances malignant character, and elevates metastatic risk. The plasma membrane organizing protein caveolin-1 (Cav1) is increased in a variety of cancers, including hepatocellular carcinoma (HCC), where it contributes to metastatic capability. However, the reason for elevation of Cav1 in tumor cells and the mechanistic basis for its contributions to metastatic risk are not fully understood. Here, we show that in HCC cells, hypoxia elevates expression of Cav1, which then acts through the calcium-binding protein S100P to promote metastasis. Hypoxic regions of HCC xenografts displayed elevated expression of Cav1. Hypoxia promoted HCC cell migration and invasion and distant pulmonary metastases, whereas Cav1 silencing abolished these effects. Gene expression profiling revealed that hypoxia-induced Cav1 functioned as a positive regulator of S100P via activation of the NF-κB pathway. S100P elevation under hypoxic conditions was abrogated by silencing of Cav1 or NF-κB function. Conversely, restoring S100P in Cav1-silenced cells rescued the migratory potential of HCC cells along with tumor formation and lung metastasis. In clinical specimens of HCC, we observed S100P overexpression to correlate with venous invasion, microsatellites, direct liver invasion, and absence of tumor encapsulation. Collectively, our findings demonstrated how hypoxia-induced expression of Cav1 in HCC cells enhances their invasive and metastatic potential. Cancer Res; 76(24); 7242–53. ©2016 AACR.
The Master Neural Transcription Factor BRN2 Is an Androgen Receptor–Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer
Authors: Bishop Jennifer L. , Thaper Daksh , Vahid Sepideh , Davies Alastair , Ketola Kirsi , Kuruma Hidetoshi , Jama Randy , Nip Ka Mun , Angeles Arkhjamil , Johnson Fraser , Wyatt Alexander W. , Fazli Ladan , Gleave Martin E. , Lin Dong , Rubin Mark A. , Collins Colin C. , Wang Yuzhuo , Beltran Himisha , Zoubeidi Amina
Published: October 2016

Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences of treatment-induced suppression of the androgen receptor (AR), remain elusive. Using a unique model of AR pathway inhibitor–resistant prostate cancer, we identified AR-dependent control of the neural transcription factor BRN2 (encoded by POU3F2) as a major driver of NEPC and aggressive tumor growth, both in vitro and in vivo. Mechanistic studies showed that AR directly suppresses BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2. Underscoring its inverse correlation with classic AR activity in clinical samples, BRN2 expression was highest in NEPC tumors and was significantly increased in castration-resistant prostate cancer compared with adenocarcinoma, especially in patients with low serum PSA. These data reveal a novel mechanism of AR-dependent control of NEPC and suggest that targeting BRN2 is a strategy to treat or prevent neuroendocrine differentiation in prostate tumors.

Significance: Understanding the contribution of the AR to the emergence of highly lethal, drug-resistant NEPC is critical for better implementation of current standard-of-care therapies and novel drug design. Our first-in-field data underscore the consequences of potent AR inhibition in prostate tumors, revealing a novel mechanism of AR-dependent control of neuroendocrine differentiation, and uncover BRN2 as a potential therapeutic target to prevent emergence of NEPC. Cancer Discov; 7(1); 54–71. ©2016 AACR.

This article is highlighted in the In This Issue feature, p. 1
Assessment of the Clinical Performance of Platelet Concentrates Treated by Pathogen Reduction Technology in Santiago de Compostela
Authors: Vilariño M. Dolores , Castrillo Azucena , Campos Alfredo , Kilian Rachel , Villamayor Mercedes , Cardoso Marcia
Published: October 2016

Introduction: This study assessed the feasibility, performance, and safety of Mirasol®-treated platelet concentrates (M-PC) stored for up to 7 days. Methods: This prospective observational study was approved by the ethical committee of the University Clinic of Santiago de Compostela. Informed consent was asked from patients receiving M-PC. M-PCs were treated with the Mirasol system according to the manufacturer's instructions. Thrombocytopenic patients were transfused according to the Spanish transfusion guidelines. Post-transfusion platelet counts were measured at 1 h and/or 24 h after transfusion. Post-transfusion surveillance of patients was maintained during the study. Results: Data from 54 evaluable patients and 135 transfusions were analyzed. The mean age of patients was 58 years. The mean age of M-PC at transfusion was 3.6 days. The mean platelet dose was 3.7 × 1011. The transfusion responses measured as mean corrected count increment 1 h after transfusion (CCI1h) and CCI24h were 9,659 and 4,751, respectively. 65% of transfusions resulted in CCI1h values ≥ 7,500. 51% of transfusions resulted in CCI24h values ≥ 4,500. Conclusion: The use of M-PC in the supportive treatment proved to be safe and effective for this cohort of thrombocytopenic patients.
Transplantation of Autologous Bone Marrow Mononuclear Cells Regulates Inflammation in a Rabbit Model of Carotid Artery Atherosclerosis
Authors: Cui Kefei , Wang Min , Yu Lie , Ren Xiao , Cui Hui , Yu Xiao Fang , Hou Suyun , Fu Chao , Wang Jian
Published: October 2016

Objective: It is well known that inflammation plays key roles in the development of atherosclerosis and that the transplantation of bone marrow mononuclear cells (BMMNCs) can suppress inflammation in rodent models of ischemic diseases. Here, we explored whether transplantation of autologous BMMNCs could prevent the progression of atherosclerosis by the alleviation of inflammatory responses in a rabbit model of carotid artery atherosclerosis. Methods and Results: The atherosclerotic rabbit model was established by air desiccation followed by a high-cholesterol diet for 8 weeks. Then, 1 × 107 BMMNCs labeled with BrdU or an equal volume of vehicle were injected into the rabbits via the ear vein. Using an ultrasonographic imaging method, we found that autologous BMMNC treatment significantly decreased the area of atherosclerotic plaques compared to the vehicle-treated group (p < 0.05). The results were further confirmed by hematoxylin-eosin staining. RT-PCR results demonstrated that BMMNC treatment significantly reduced the expression of interleukin (IL)-6 and CD147 but increased the expression of IL-10 and transforming growth factor-β compared with vehicle treatment (p < 0.05), which was consistent with Western blot results. Conclusions: Transplantation of autologous BMMNCs delays the development of atherosclerosis, most probably via the attenuation of inflammatory responses, which could be a new approach for treating carotid atherosclerosis.
In vitro and in vivo Pharmacodynamics of Colistin and Aztreonam Alone and in Combination against Multidrug-Resistant Pseudomonas aeruginosa
Authors: Yamagishi Yuka , Hagihara Mao , Kato Hideo , Hirai Jun , Nishiyama Naoya , Koizumi Yusuke , Sakanashi Daisuke , Suematsu Hiroyuki , Nakai Hazuki , Mikamo Hiroshige
Published: October 2016

Background: Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study. Methods: We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model. Results: The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy. Conclusion: The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.
Overexpression of Intrarenal Renin-Angiotensin System in Human Acute Tubular Necrosis
Authors: Cao Wei , Jin Lingwei , Zhou Zhanmei , Yang Manqiu , Wu Chunyi , Wu Liling , Cui Shuang
Published: October 2016

Background/Aims: Acute tubular necrosis (ATN), a leading cause of acute kidney injury (AKI), is associated with decreased survival and increased progression of chronic kidney disease. A barrier to improving the clinical outcomes is the incomplete understanding of the pathogenesis of AKI. Our objective is to test the hypothesis that intrarenal renin-angiotensin system (RAS) is overexpressed in patients with ATN and could be an indicator of ATN severity. Methods: A transversal study was conducted in patients with biopsy-proven ATN. Intrarenal expression of angiotensinogen and angiotensin II, and urinary angiotensinogen were measured. Results: Patients with ATN demonstrated upregulation of intrarenal RAS, evidenced by upregulation of intrarenal angiotensinogen and angiotensin II. Patients with ATN also have elevated urinary angiotensinogen level that correlated with the overexpressed intrarenal RAS. Moreover, this increase in intrarenal RAS expression and urinary angiotensinogen was associated with the extent of acute tubular injury and urinary albumin excretion, respectively. Conclusions: We demonstrate that the intrarenal RAS is upregulated in patients with ATN and is associated with the severity of ATN. Urinary angiotensinogen reflects intrarenal RAS status, and is of value to assess the severity of ATN.
Vancomycin Trough and Acute Kidney Injury: A Large Retrospective, Cohort Study
Authors: Hammoud Kassem , Brimacombe Michael , Yu Alan , Goodloe Neil , Haidar Wael , El Atrouni Wissam
Published: October 2016

Background: The association between vancomycin trough (VT) and acute kidney injury (AKI) at the recommended doses remains controversial. Methods: The authors conducted a retrospective, observational cohort study of 500 adult patients who received vancomycin for ≥72 h. Data collected included 2 main predictors: average VT (including only VTs before the occurrence of AKI), first VT and other possible risk factors for AKI. The baseline characteristics/variables between patients with AKI and patients with no AKI were compared. Logistic regression models were used to develop multivariate models. The authors divided the patients into 4 subgroups: (1) VT <10, (2) 10 ≤ VT < 15, (3) 15 ≤ VT < 20 and (4) VT ≥20 µg/ml. All subgroups were compared to subgroup 2 (reference group). Results: AKI occurred in 12.85% of patients while on vancomycin. The incidence of AKI in subgroups 1-4 was 8.02, 13.61, 13.70 and 31.82%, respectively, using the first VT, that is significantly higher in subgroup 4. Using average VT, AKI incidence was 5, 10.38, 19.01 and 25.58%, respectively, that is significantly higher in subgroups 3 and 4. On multivariate logistic regression, average VT, first VT, average VT >15, first VT >15, methicillin-resistant Staphylococcus aureus infection and morbid obesity were significantly associated with increased incidence of AKI. Conclusion: Clinicians should be careful when aiming for a VT >15 μg/ml as this is associated with increased incidence of AKI.
CD70 limits atherosclerosis and promotes macrophage function
Authors: Lievens Dirk , Engel David , Spitz Charlotte , Bürger Christina , Rinne Petteri , Beckers Linda , Dandl Angelika , Reim Sigrid , Ahmadsei Maiwand , Van den Bossche Jan , Holdt Lesca M. , Megens Remco T. A. , Schmitt Martin M. , de Winther Menno , Biessen Eric A. , Borst Jannie , Faussner Alexander , Weber Christian , Winkels Holger , Meiler Svenja , Smeets Esther , Lutgens Esther , Gerdes Norbert
Published: October 2016

The costimulatory molecule CD70 is expressed on activated immune cells and is known to modulate responses of T, B, and NK cells via its receptor CD27. Until now, there is only limited data describing the role of CD70 in atherosclerosis. We observed that ruptured human carotid atherosclerotic plaques displayed higher CD70 expression than stable carotid atherosclerotic plaques, and that CD70 expression in murine atheroma localized to macrophages. Lack of CD70 impaired the inflammatory capacity (e. g. reactive oxygen species and nitric oxide production) of bone marrow-derived macrophages, increased both M1-like and M2-like macrophage markers, and rendered macrophages meta-bolically inactive and prone to apoptosis. Moreover, CD70-deficient macrophages expressed diminished levels of scavenger receptors and ABC-transporters, impairing uptake of oxidised low-density lipoprotein (oxLDL) and cholesterol efflux, respectively. Hyperlipidaemic Apoe −/− mice reconstituted with CD70-deficient bone marrow displayed a profound increase in necrotic core size, plaque area, and number of lesional macrophages as compared to mice receiving control bone marrow. Accordingly, 18 week-old, chow diet-fed CD70-deficient Apoe−/−mice displayed larger atheroma characterised by lower cellularity and more advanced plaque phenotype than Apoe−/− mice. In conclusion, CD70 promotes macrophage function and viability and is crucial for effective phagocytosis and efflux of oxLDL. Deficiency in CD70 results in more advanced atheroma. Our data suggest that CD70 mitigates atherosclerosis at least in part by modulating macrophage function.

Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Coagulation factor XII induces pro-inflammatory cytokine responses in macrophages and promotes atherosclerosis in mice
Authors: Manthey Helga D. , Cochain Clement , Busch Martin , Chaudhari Sweena M. , Stegner David , Yepes Manuel , Lorenz Kristina , Nolte Marc W. , Nieswandt Bernhard , Vorlova Sandra , Koch Miriam , Zernecke Alma
Published: October 2016

Atherosclerosis is considered a chronic inflammatory disease of the vessel wall. Coagulation pathways and immune responses contribute to disease development. The role of coagulation factor XII (FXII) in vascular inflammation, however, remains controversial. We here investigated the function of FXII in atherosclerosis using apolipoprotein E and FXII-deficient (F12−/−Apoe −/−) mice. Compared to F12 +/+ Apoe −/− controls, atherosclerotic lesion formation was reduced in F12−/−Apoe −/− mice. This was associated with a decrease in serum interleukin (IL)-1β and IL-12 levels and reduced expression of pro-inflammatory cytokines in the aorta in atherosclerotic F12−/−Apoe −/− mice, as well as diminished Th1-cell differentiation in the aorta, blood, and lymphoid organs. No changes in circulating bradykinin, thrombin-antithrombin-complexes or plasminogen were observed. Mechanistically, activated FXII (FXIIa) was revealed to directly induce bone marrow-derived macrophages to secrete pro-inflammatory cytokines, including tumour necrosis factor-α, IL-1β, IL-12, and IL-6. Exposure of bone marrow-derived antigen presenting cells to FXIIa similarly induced pro-inflammatory cytokines, and an enhanced capacity to trigger antigen-specific interferon γ-production in CD4+ T cells. Notably, bone-marrow derived macrophages were capable of directly activating FXII. Moreover, the induction of cytokine expression by FXIIa in macrophages occurred independently of FXII protease enzymatic activity and was decreased upon phospholipase C treatment, suggesting urokinase-type plasminogen activator receptor (uPAR) to confer FXIIa-induced cell signalling. These data reveal FXII to play an important role in atherosclerotic lesion formation by functioning as a strong inducer of pro-inflammatory cytokines in antigen-presenting cells. Targeting of FXII may thus be a promising approach for treating cardiovascular disease.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Serum 25-hydroxyvitamin D and the risk of stroke in Hong Kong Chinese
Authors: Sing Chor-Wing , Cheung Bernard M. Y. , Wong Ian C. K. , Tan Kathryn C. B. , Kung Annie W. C. , Leung Raymond Y. H. , Han Yi , Cheung Ching-Lung
Published: October 2016

Low vitamin D levels have been associated with various cardiovascular diseases; however, whether it is associated with stroke remains inconclusive. We aimed to evaluate the association between serum 25-hydroxyvitamin D and risk of stroke. We conducted a cohort study consisting of 3,458 participants from the Hong Kong Osteoporosis Study aged ≥45 at baseline, examined between 1995 and 2010 and followed up using electronic medical records. Ischaemic and haemorrhagic stroke were defined using the ICD-9 code. In multivariable Cox-proportional hazard regression, quintiles 1 and 4 were significantly associated with increased risk of stroke when compared to the highest quintile (Quintile 1: HR, 1.78; 95 % CI, 1.16–2.74 and quintile 4: HR, 1.61; 95 % CI, 1.07–2.43). A similar association was observed in both men and women. In subgroup analysis, the association was specifically observed for ischaemic stroke, but not haemorrhagic stroke. Using a penalized regression spline, the association between vitamin D and risk of stroke was in a reverse J-shape, with the lowest risk of stroke being observed at 25(OH)D levels between 70 and 80 nmol/l. In conclusion, a low vitamin D level is associated with increased risk of ischaemic stroke; however, whether high vitamin D level is also associated with increased risk of stroke requires further study.

Supplementary Material to this article is available at www.thrombosis-online.com.
Integrative review of literature on the construction of Therapeutic Projects Singles in the mental health field
Authors: Rodovalho Ana Laura Pires , Pegoraro Renata Fabiana
Published: October 2016

Realizou-se uma revisão integrativa de literatura sobre a construção e o acompanhamento dos Projetos Terapêuticos Singulares pelas equipes dos Centros de Atenção Psicossocial. O levantamento foi realizado nas bases eletrônicas Scielo, Redalyc e Pepsic entre 2004 e 2014. Foram encontradas 419 publicações e selecionadas 13 a partir das palavras-chave: projetos terapêuticos singulares, projetos terapêuticos individuais, saúde mental, atenção psicossocial, técnico de referência, Centro de Atenção Psicossocial, serviços de saúde mental. A análise dos resultados dos artigos permitiu identificar quatro blocos de sentido: Quem elabora o projeto; Problemas na elaboração; Relevância do projeto; e sua inexistência. O estudo aponta para dificuldades na inclusão de familiares e usuários na construção dos projetos terapêuticos pelas equipes
AVALIAÇÃO DA SATISFAÇÃO DOS USUÁRIOS DE UM SERVIÇO DE SAÚDE PÚBLICO-PRIVADO NO NORDESTE DO BRASIL E A JUDICIALIZAÇÃO DA SAÚDE
Authors: Silva Junior Geraldo Bezerra da , Dias Eduardo Rocha
Published: October 2016

Este artigo tem por escopo analisar o grau de satisfação dos usuários de um serviço público-privado de saúde do Nordeste do Brasil, bem como o nível de conhecimento sobre seus direitos e a procura pelo Judiciário para garanti-los. Foram avaliadas as respostas dadas a um questionário aplicado junto a 67 pacientes atendidos pelo Núcleo de Assistência Médica Integrada, da Universidade de Fortaleza, conveniado ao Sistema Único de Saúde (SUS). Os pacientes entrevistados mostraram satisfação com os serviços oferecidos, considerando-os como bons ou excelentes. O principal problema evidenciado foi a dificuldade de acesso a medicações fornecidas pelo SUS e a falta de conhecimento dos direitos relacionados à saúde. Observou-se uma baixa procura pela Justiça para questões ligadas à saúde, o que pode se explicar, por um lado, pelo reduzido grau de conhecimento dos direitos relacionados a tal campo e pela baixa escolaridade da maior parte dos entrevistados. A melhora do grau de satisfação pode contribuir para reduzir a judicialização, muito embora usuários mais bem informados possam se mostrar mais exigentes e recorrer mais à Justiça. Soluções alternativas de resolução de conflitos, como a mediação e a justiça restaurativa, podem contribuir para diminuir a busca pelo Judiciário.
BREVES CONSIDERAÇÕES ACERCA DO CONTROLE JURISDICIONAL DE POLÍTICAS PÚBLICAS EM FACE DO DIREITO FUNDAMENTAL AO MEIO AMBIENTE ECOLOGICAMENTE EQUILIBRADO
Authors: Myszczuk Ana Paula , Meirelles Jussara Maria Leal de
Published: October 2016

O presente artigo tem por objetivo realizar um breve comento sobre o Recurso Especial n. 1.367.549 – MG (2011/0132513-5), julgado pelo Superior Tribunal de Justiça, que analisa a possibilidade da utilização do controle judicial de políticas públicas em face de falta de prestações positivas por parte da Administração Pública na área ambiental. Dessa forma, o artigo apresenta um resumo comentado da decisão e traça algumas considerações sobre as políticas públicas municipais. Além disso, discute a possibilidade do uso do controle judicial de políticas públicas em face de direitos fundamentais e, por fim, o papel do Ministério Público no controle social de políticas públicas.
TODO, PARA TODOS Y GRATIS: COORDENADAS PARA GARANTIZAR LA INVIABILIDAD DE UN SISTEMA DE SALUD
Authors: Pregno Elian
Published: October 2016

El presente trabajo pretende anotar el fallo de la Corte Suprema de Justicia de la Nación Argentina recaído en autos caratulados: "Asociación Civil para la Defensa en el Ámbito Federal e Internacional de Derechos c/ Instituto Nacional de Servicios Sociales para Jubilados y Pensionados s/ amparo", en febrero de 2015. En primer término, se ofrece -en apretada síntesis- una referencia al caso, esclareciendo: las partes en litigio; la pretensión de la parte actora; el medio procesal interpuesto y la secuencia seguida en las sucesivas instancias, como así también los argumentos esgrimidos en cada una de ellas. A este último respecto, cabe destacar que el máximo tribunal argentino ha sentado como doctrina que resultan procedentes las acciones de clase interpuestas con el objeto de que el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados brinde cobertura integral de prestaciones a personas con discapacidad, beneficiarias de pensiones no contributivas. En segundo lugar, se presenta la integración del sistema de salud en la Argentina y una serie de conjeturas en orden a la tensa relación que exhiben la justicia y la utilidad a la hora de fundamentar los derechos humanos -en general- y el derecho a la atención de la salud -en particular-.
ACIDENTES DE TRÂNSITO E DIREITO À SAÚDE: PREVENÇÃO DE VIDAS E ECONOMIA PÚBLICA
Authors: Massaú Guilherme Camargo , Rosa Rosana Gomes da
Published: October 2016

Os acidentes de trânsito constituem significativa fonte de despesas na gestão da saúde pública brasileira. Em contrapartida, sua prevenção representa importante ato de gestão da saúde pública, tanto pela redução de gastos diretos no Sistema Único de Saúde (SUS), como pela redução das despesas indiretas junto ao sistema de seguridade social, às vítimas e seus familiares e ao sistema econômico em geral. Este artigo tem como objetivo demonstrar que a garantia do direito à saúde é um desafio agravado pelas despesas destinadas ao atendimento e tratamento das vítimas de acidentes de trânsito. Busca, ainda, estabelecer a importância da efetivação das dimensões da prevenção, enquanto dever do Estado, em termos jurídicos de acesso à saúde. O método utilizado é a análise bibliográfica, a fim de situar o problema da efetivação do direito à saúde de forma preventiva, com impacto no orçamento do Estado-Administração. O método quantitativo contribuiu para que se pudesse visualizar a importância da prevenção como política social de saúde pública, principalmente no trânsito e nas estradas brasileiras. Assim, foi possível estabelecer uma projeção de gastos públicos para recuperação da saúde, bem como demonstrar a repercussão dos acidentes de trânsito nas contas públicas, de modo a relacionar as políticas públicas preventivas de acidentes com a manutenção e a preservação da saúde dos indivíduos. Trata-se de uma prevenção com duplo viés: economia financeira e economia de recursos humanos.
AUTONOMIA DA VONTADE DO PACIENTE E CAPACIDADE PARA CONSENTIR: UMA REFLEXÃO SOBRE A COAÇÃO IRRESISTÍVEL
Authors: Beltrão Silvio Romero
Published: October 2016

O presente trabalho pretende investigar a validade da manifestação de vontade do paciente, no momento em que o mesmo está influenciado pela dor e pelo sofrimento e necessita declarar se irá se submeter ou não a determinado tratamento. A pesquisa tem caráter interdisciplinar e se utiliza dos elementos da Teoria Geral do Direito Civil para a declaração de validade do negócio jurídico. A relação médico-paciente necessita de uma visão completa quanto aos elementos e requisitos que constituem sua validade na ordem jurídica. Como ponto de partida, analisa a relação do médico com os pacientes adeptos da religião Testemunha de Jeová para, em seguida, verificar os requisitos de validade da declaração de vontade. Investiga a manifestação da vontade como principal elemento do negócio jurídico para, no final, definir os conflitos que envolvem o estudo da autonomia da vontade e a dificuldade de solução dos casos concretos.
Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat
Authors: Fu Jinjuan , Han Yu , Wang Jialiang , Liu Yukai , Zheng Shuo , Zhou Lin , Jose Pedro A. , Zeng Chunyu
Published: October 2016

Background

Exercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure.

Methods and Results

Blood pressures of male Wistar‐Kyoto (
WKY)
rats and spontaneously hypertensive rats (
SHR
s) were monitored through the carotid artery. Our study found that acute intravenous injection of irisin reduced blood pressure in
SHR
s, but not
WKY
rats. Irisin, by itself, had no direct vasorelaxing effect in phenylephrine‐preconstricted mesenteric arteries from
SHR
s. However, irisin augmented the acetylcholine‐induced vasorelaxation in mesenteric arteries from
SHR
s that could be reversed by Nω‐nitro‐
l
‐arginine‐methyl ester (L‐
NAME;
100 μmol/L), indicating a role of nitric oxide (
NO)
in this action. Indeed, irisin increased
NO
production and phosphorylation of endothelial nirtic oxide synthase (
eNOS)
in endothelial cells. 5′‐
AMP
‐activated protein kinase (
AMPK
) was involved in the vasorelaxing effect of irisin because compound C (20 μmol/L), an
AMPK
inhibitor, blocked the irisin‐mediated increase in phosphorylation of
eNOS
and protein kinase B (Akt) in endothelial cells and vasodilation in mesenteric arteries.

Conclusions

We conclude that acute administration of irisin lowers blood pressure of
SHR
s by amelioration of endothelial dysfunction of the mesenteric artery through the
AMPK
‐Akt‐
eNOS
‐
NO
signaling pathway.
Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats
Authors: Ali El‐Basyuni Yousra , Li Yuan , Anand‐Srivastava Madhu B.
Published: October 2016

Background

We previously showed that the levels of both Giα‐2 and Giα‐3 proteins were augmented in spontaneously hypertensive rats (
SHRs
) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hypertension in
SHRs
. The aim of the present study was to determine the specific contributions of Giα‐2 and Giα‐3 proteins to the development of hypertension.

Methods and Results

Antisense oligodeoxynucleotide of Giα‐2 and Giα‐3 encapsulated in
PEG
/
DOTAP
/
DOPE
cationic liposomes were administrated intravenously into 3‐week‐old prehypertensive
SHRs
and Wistar Kyoto rats, whereas the control Wistar Kyoto rats and
SHRs
received PBS, empty liposomes, or sense. The knockdown of Giα‐2 but not Giα‐3 protein attenuated tachycardia and prevented the development of hypertension up to age 6 weeks; thereafter, blood pressure started increasing and reached the same level as that of untreated
SHRs
at 9 weeks. Furthermore, Giα‐2 and Giα‐3 antisense oligodeoxynucleotide treatments significantly decreased the enhanced levels of Giα‐2 and Giα‐3 proteins, respectively, and enhanced levels of superoxide anion and
NADPH
oxidase activity in heart, aorta, and kidney and hyperproliferation of vascular smooth muscle cells from SHRs aged 6 weeks. In addition, antisense oligodeoxynucleotide treatment with Giα‐2 but not Giα‐3 restored enhanced inhibition of adenylyl cyclase by oxotremorine to WKY levels.

Conclusions

These results suggested that the enhanced expression of Giα‐2 but not Giα‐3 protein plays an important role in the pathogenesis of hypertension and tachycardia in
SHRs
.
Introduction: Art Periodicals Today, Historically Considered
Authors: Eşanu Octavian , Harutyunyan Angela
Published: October 2016

The Introduction to the Special Issue entitled Art Periodicals, Historically Considered sketches an outline of the advent of periodicals in the context of the Enlightenment demand for the public use of reason, and situates the emergence of art periodicals in the context of the advent of autonomous art since the 19th century. The article introduces the contributions to the Special Issue and opens up a way to reposition the question of critique in today's art publishing.
Realizing the un’s Protection Promise: A Central Challenge for the Next Secretary-General
Authors: von Einsiedel Sebastian , Bosetti Louise
Published: October 2016

Today the relevance, legitimacy and credibility of the United Nations are widely seen as a function of its efforts to end civil wars and prevent the worst mass atrocities. Despite advances in recent years, the un’s protection record over the past decade is mixed. Considering the ever-growing global expectations of the un to protect populations from large-scale violence, along with a rise in protection risks, these issues will naturally feature highly on the agenda of António Guterres when he assumes the post of Secretary-General in January 2017. He will need to overcome a number of daunting challenges to ensure the un realizes its protection promise and restores the organization’s damaged credibility in this area. To achieve this, he will need to make progress on three fronts in particular: first, fostering a renewed consensus around the Responsibility to Protect norm; second, strengthening the ability of peace operations to implement protection mandates while ensuring that expectations are in line with what blue helmets can deliver; and third, improving the un’s response to severe human rights violations in non-mission settings.
Tracing the Evolution and Economic Potential of Konjac Glucomannan in Amorphophallus species (Araceae) using Molecular Phylogeny and RAPD Markers
Authors: MEKKERDCHOO ORACHORN , BOROMPICHAICHARTKUL CHALEEDA , PERRIGO ALLISON , SRZEDNICKI GEORGE , PRAKITCHAIWATTANA CHEUNJIT , ANTONELLI ALEXANDRE
Published: October 2016

The genus Amorphophallus is an economically important taxon that is abundant in Old World tropical forests (Asia, Oceania and Africa). It includes many species that are used with increasing frequency as a source of food and pharmaceutical products worldwide. Amorphophallus konjac is an important economic crop and has been used widely in China and Japan for commercial konjac glucomannan (KGM) production. However, the species’ range does not extend to Thailand, where other closely related species may be more suitable for commercial KGM production. Present understanding of genetic relationships among Thai Amorphophallus species is still limited, and the connection between evolutionary history and KGM content is unknown. Here, the genetic relationships among various accessions of Amorphophallus spp. collected in Thailand are investigated using the chloroplast trnL-trnF spacer, nuclear ribosomal internal transcribed spacer (ITS) region and the second intron of LEAFY (FLint2) together with genome-wide DNA variation analysis, Randomly Amplified Polymorphic DNA (RAPD) technique. RAPD primers are also developed to quickly and efficiently identify species producing high levels of KGM. This study finds that two monophyletic clades include high KGM content species. RAPD analyses indicate that primer AC-10 generates specific bands identifying species belonging only to the high and medium KGM content clades.  These primers can be used as a screening tool for economical species, aiming at improving the industrial production of KGM in Thailand and the world.
Impatiens pseudocitrina (Balsaminaceae), a new species from Arunachal Pradesh, Northeast India
Authors: HAREESH VADAKKOOT SANKARAN , GOGOI RAJIB , SABU MAMIYIL
Published: October 2016

Impatiens pseudocitrina from Anjaw district, Arunachal Pradesh, North-East India, is newly described and illustrated. Detailed descriptions, distribution, and ecological information, along with colour photographs and key to the closely related species, are provided for identification of the species.