bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Dependence of Reverse Simulation for Identifying a Pollutant Source on Grid Resolution and Filter Width in Cavity Flow
Authors: Abe Satoshi , Kato Shinsuke , Hamba Fujihiro , Kitazawa Daisuke
Published: May 2012

When a hazardous substance is diffused, it is necessary to identify the pollutant source and respond immediately. However, there are many cases in which damage is caused without a clear understanding of where the pollutant source is located. There are three groups of identifying pollutant source information (Liu and Zhai, 2007): the probability method, forward method, and backward method. In our previous study, we proposed reverse simulation, which is categorized as a backward method (Abe and Kato, 2011). Numerical instability by negative diffusion is a principal problem in the backward method. In order to improve the problem, we applied a low‐pass filter operation to the concentration flux in the RANS analysis. The simulation secured the numerical stability. However, reverse simulation accuracy is expected to depend on the grid resolution and filter width. In this paper, we introduce reverse simulation results in cavity flow. In particular, we survey the dependence of reverse simulation accuracy on the grid resolution and filter width. Moreover, we discuss the dependence of reverse simulation on the grid resolution and filter width with a one‐dimensional diffusion equation. As a result, we found that the simulated negative diffusion varies greatly among the grid resolution and filter width.
Improved Virtual Potential Field Algorithm Based on Probability Model in Three-Dimensional Directional Sensor Networks
Authors: Huang Junjie , Sun Lijuan , Wang Ruchuan , Huang Haiping
Published: May 2012

In conventional directional sensor networks, coverage control for each sensor is based on a 2D directional sensing model. However, 2D directional sensing model failed to accurately characterize the actual application scene of image/video sensor networks. To remedy this deficiency, we propose a 3D directional sensor coverage-control model with tunable orientations. Besides, a novel criterion for judgment is proposed in view of the irrationality that traditional virtual potential field algorithms brought about on the criterion for the generation of virtual force. Furthermore, cross-set test is used to determine whether the sensory region has any overlap and coverage impact factor is introduced to reduce profitless rotation from coverage optimization, thereby the energy cost of nodes was restrained and the performance of the algorithm was improved. The extensive simulations results demonstrate the effectiveness of our proposed 3D sensing model and IPA3D (improved virtual potential field based algorithm in three-dimensional directional sensor networks).
White Matter Hyperintensities Are an Independent Predictor of Physical Decline in Community-Dwelling Older People
Authors: Zheng Jacqueline J.J. , Delbaere Kim , Close Jacqueline C.T. , Sachdev Perminder , Wen Wei , Brodaty Henry , Lord Stephen R.
Published: May 2012

Background: Ageing is associated with physical disability, but little is known about the influence of white matter hyperintensities (WMHs) on physical function decline in older people. Objective: To investigate the role of WMHs as a predictor of decline in physical function in cognitively intact older people. Methods: 287 community-dwelling people aged 70–90 years underwent the Physiological Profile Assessment (PPA) and assessments of total and regional WMH volumes, cognitive function and comorbidities. Participants underwent reassessment of the PPA 12 months later, and those in the top quartile for increases in PPA scores over the year were regarded as having declined physically. Results: Multivariate logistic regression analyses revealed that people with WMH volumes in the 4th quartile showed greater physical decline (odds ratio 3.02, 95% confidence interval 1.02–8.95) while controlling for age, baseline physical function, general health, physical activity and cognitive function. Subsequent univariate analyses indicated that WMHs in the deep fronto-parietal and periventricular parieto-occipital regions had the strongest associations with physical decline. Conclusions: These findings indicate that WMHs are an independent predictor of decline in physical function and suggest that interventions that focus on preventing the development or progression of white matter lesions may help preserve physical function in older people.
Tumor Markers in Clinical Practice: A Review Focusing on Common Solid Cancers
Authors: Duffy Michael J.
Published: May 2012

Tumor markers are playing an increasingly important role in cancer detection and management. These laboratory-based tests are potentially useful in screening for early malignancy, aiding cancer diagnosis, determining prognosis, surveillance following curative surgery for cancer, up front predicting drug response or resistance, and monitoring therapy in advanced disease. Clinically useful markers include fecal occult blood testing in screening for early colorectal cancer, carcinoembryonic antigen in the management of patients with colorectal cancer, both α-fetoprotein and human chorionic gonadotrophin in the management of patients with non-seminomatous germ cell tumors, CA 125 for monitoring therapy in patients with ovarian cancer, estrogen receptors for predicting response to hormone therapy in breast cancer, human epidermal growth factor receptor 2 for the identification of women with breast cancer likely to respond to trastuzumab (Herceptin) and KRAS mutational status for identifying patients with advanced colorectal cancer likely to benefit from treatment with the anti-epidermal growth factor receptor antibodies, cetuximab and panitumumab. Although widely used, the value of prostate-specific antigen screening in reducing mortality from prostate cancer is unclear.
Surgical Management of Tympanojugular Paragangliomas with Intradural Extension, with a Proposed Revision of the Fisch Classification
Authors: Sivalingam Shailendra , Konishi Masaya , Shin Seung-Ho , Lope Ahmed Raja Ahmed R. , Piazza Paolo , Sanna Mario
Published: May 2012

Background: Tympanojugular paragangliomas (TJPs) with intradural extension can be successfully treated by a single or staged procedure with low surgical morbidity. Objectives: To present the clinical findings and treatment methods used for surgically treating TJP with intradural extension, as well as to discuss the complications of treatment and the relative merits of single versus staged surgery by using a comprehensive literature review comparing objective outcome measures. Study Design: A retrospective case review of 45 cases of TJP with intradural extension. Setting: A quaternary skull base and neurotologic center. Materials and Methods: The charts of 45 patients with Fisch classification class C or D TJP with intradural extension, who were operated on from April 1988 to April 2010, were analyzed. Clinical findings and preoperative lower cranial nerve (LCN) palsy as well as postoperative totality of resection, postoperative LCN palsy and complications were studied. The types, indications, and distribution of staged procedures were also analyzed. Results: Out of 45 cases, 22 were C3di2. The IX and X cranial nerves were the commonest nerves affected preoperatively. Preoperative internal carotid artery management was performed in 16 cases. Twenty-nine cases had a single procedure and 16 had a staged procedure. The main indication for staged procedures was intradural extension of 2 cm or more. The infratemporal fossa approach (ITFA) type A was the main procedure in all cases. Overall, total resection was achieved in 68.8% of cases with postoperative cerebrospinal fluid leak in 4.4% cases. Postoperative House-Beckmann grade I–III facial nerve status was maintained in 80% of cases, and overall LCN preservation rate was 56.9%. There were no cases requiring tracheostomy, and 3 cases required delayed phonosurgical procedures to improve their voice. Conclusions: TJP with intradural extension can be successfully managed with the judicious use of staged procedures to reduce the incidence of postoperative cerebrospinal fluid leak. The ITFA did not cause an excessively high rate of facial nerve palsy, and the overall total resection and LCN preservation rate compares very favorably with previously published data.
Autologous Fat Transfer for Face Rejuvenation with Tumescent Technique Fat Harvesting and Saline Washing: A Report of 215 Cases
Authors: Rusciani Scorza Antonio , Rusciani Scorza Luigi , Troccola Antonietta , Micci Daniela Maria , Rauso Raffaele , Curinga Giuseppe
Published: May 2012

Various materials have been used for tissue augmentation and for the treatment of rhytids. Autologous fat transfer (AFT) is considered ideal regarding biocompatibility and patient concerns. This study was performed on a series of 215 female patients for face rejuvenation with tumescent technique fat harvesting and saline washing. The study was based on two AFT procedures for each patient. Second treatment was performed at least 1 month after the first operation. Their mean age was 55.5 ± 2.1 years. High-definition photographs in five standard views, front (n = 1), side (n = 2) and oblique of 3/4 (n = 2), were taken for the preoperative morphological study. Aesthetic outcomes were evaluated by the operating surgeon, the patient and an independent dermatologist. Outcomes were evaluated by comparing the preoperative photographs with those taken 1 month after the first procedure and at the end of the 1-year follow-up period. At 12 months all the patients except one noted an improvement. Of these 85.6% (184 patients) were satisfied with the treatment. The operating surgeon and the independent observer noted respectively a sufficient correction in 88.8 and 95.3%. AFT was considered painless by 94.9% and slightly painful by 5.1% of subjects. Fat tissue harvesting by tumescent anesthesia and purification with saline washing enable adipocyte viability to be preserved throughout the procedure and to perform the treatment under local anesthesia.
Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome
Authors: Athanasakis E. , Fabretto A. , Faletra F. , Mocenigo M. , Morgan A. , Gasparini P.
Published: May 2012

Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the COH1 gene. It is characterized by intellectual disability, hypotonia, joint hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some cases, intermittent isolated neutropenia. We investigated an Italian patient with CS together with his family. Genetic analysis disclosed 2 novel mutations: the first is an intronic mutation (c.8697–9A>G) creating a new splice site 8 nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA) generating a premature stop codon. The compound heterozygous mutations explain the proband’s phenotype and improved the knowledge of genotype-phenotype correlation.
Neural Control of Ventricular Rate in Ambulatory Dogs With Pacing-Induced Sustained Atrial Fibrillation
Authors: Park Hyung-Wook , Shen Mark J. , Han Seongwook , Shinohara Tetsuji , Maruyama Mitsunori , Lee Young-Soo , Shen Changyu , Hwang Chun , Chen Lan S. , Fishbein Michael C. , Lin Shien-Fong , Chen Peng-Sheng
Published: May 2012

Background—

We hypothesize that inferior vena cava–inferior atrial ganglionated plexus nerve activity (IVC-IAGPNA) is responsible for ventricular rate (VR) control during atrial fibrillation (AF) in ambulatory dogs.

Methods and Results—

We recorded bilateral cervical vagal nerve activity (VNA) and IVC-IAGPNA during baseline sinus rhythm and during pacing-induced sustained AF in 6 ambulatory dogs. Integrated nerve activities and average VR were measured every 10 seconds over 24 hours. Left VNA was associated with VR reduction during AF in 5 dogs (from 211 bpm [95% CI, 186–233] to 178 bpm [95% CI, 145–210];
P
<0.001) and right VNA in 1 dog (from 208 bpm [95% CI, 197–223] to 181 bpm [95% CI, 163–200];
P
<0.01). There were good correlations between IVC-IAGPNA and left VNA in the former 5 dogs and between IVC-IAGPNA and right VNA in the last dog. IVC-IAGPNA was associated with VR reduction in all dogs studied. Right VNA was associated with baseline sinus rate reduction from 105 bpm (95% CI, 95–116) to 77 bpm (95% CI, 64–91;
P
<0.01) in 4 dogs, whereas left VNA was associated with sinus rate reduction from 111 bpm (95% CI, 90–1250) to 81 bpm (95% CI, 67–103;
P
<0.01) in 2 dogs.

Conclusions—

IVC-IAGPNA is invariably associated with VR reduction during AF. In comparison, right or left VNA was associated with VR reduction only when it coactivates with the IVC-IAGPNA. The vagal nerve that controls VR during AF may be different from that which controls sinus rhythm.
Short- and Long-Term Outcomes With Drug-Eluting and Bare-Metal Coronary Stents
Authors: Bangalore Sripal , Kumar Sunil , Fusaro Mario , Amoroso Nicholas , Attubato Michael J. , Feit Frederick , Bhatt Deepak L. , Slater James
Published: May 2012

Background—

Drug-eluting stents (DES) have been in clinical use for nearly a decade; however, the relative short- and long-term efficacy and safety of DES compared with bare-metal stents (BMS) and among the DES types are less well defined.

Methods and Results—

PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until March 2012, that compared any of the Food and Drug Administration–approved durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary lesions, enrolling at least 100 patients and with follow-up of at least 6 months. Short-term (≤1 year) and long-term efficacy (target-vessel revascularization, target-lesion revascularization) and safety (death, myocardial infarction, stent thrombosis) outcomes were evaluated and trial-level data pooled by both mixed-treatment comparison and direct comparison analyses. From 76 randomized clinical trials with 117 762 patient-years of follow-up, compared with BMS, each DES reduced long-term target-vessel revascularization (39%–61%), but the magnitude varied by DES type (EES∼SES∼ZES-R>PES∼ZES>BMS), with a >42% probability that EES had the lowest target-vessel revascularization rate. There was no increase in the risk of any long-term safety outcomes, including stent thrombosis, with any DES (versus BMS). In addition, there was reduction in myocardial infarction (all DES except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio, 0.51; 95% credibility interval, 0.35–0.73). The safest DES appeared to be EES (>86% probability), with reduction in myocardial infarction and stent thrombosis compared with BMS. Short-term outcomes were similar to long-term outcomes, with SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being the safest stent.

Conclusions—

DES are highly efficacious at reducing the risk of target-vessel revascularization without an increase in any safety outcomes, including stent thrombosis. However, among the DES types, there were considerable differences, such that EES, SES, and ZES-R were the most efficacious and EES was the safest stent.
Increasing prevalence of ESBL production among Irish clinical Enterobacteriaceae from 2004 to 2008: an observational study
Authors: Fennell Jérôme , Vellinga Akke , Hanahoe Belinda , Morris Dearbhaile , Boyle Fiona , Higgins Francis , Lyons Maura , O’Connell Karina , Keady Deirbhile , Cormican Martin
Published: May 2012

Background

Extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae infections are associated with delayed initiation of appropriate treatment, poor outcomes and increased hospital stay and expense. Although initially associated with healthcare settings, more recent international reports have shown increasing isolation of ESBLs in the community. Both hospital and community ESBL epidemiology in Ireland are poorly defined.

Methods

This report describes clinical and laboratory data from three hospitals over 4.5 years. All significant isolates of Enterobacteriaceae were subjected to standardized antimicrobial susceptibility testing and screening for ESBL production. Available patient data from hospital databases were reviewed.

Results

The database included 974 ESBL producing organisms from 464 patients. Urine and blood isolates represented 84% and 3% of isolates respectively. E. coli predominated (90.9%) followed by K. pneumoniae (5.6%). The majority of patients (n = 246, 53.0%) had been admitted to at least one of the study hospitals in the year prior to first isolation of ESBL. The overall 30-day all-cause mortality from the date of culture positivity was 9.7% and the 1 year mortality was 61.4%. A Cox regression analysis showed age over 60, male gender and previous hospital admissions were significant risk factors for death within 30 days of ESBL isolation. Numbers of ESBL-producing E. coli isolated from urine and blood cultures increased during the study. Urine isolates were more susceptible than blood isolates. Co-resistance to other classes of antimicrobial agents was more common in ESBL producers from residents of long stay facilities (LSF) compared with hospital inpatients who lived at home.

Conclusions

This work demonstrates a progressively increasing prevalence of ESBL Enterobacteriaceae in hospital, LSF and community specimens in a defined catchment area over a long time period . These results will improve clinician awareness of this problem and guide the development of empiric antimicrobial regimens for community acquired bloodstream and urinary tract infections.
Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma
Authors: Romilda Cardin , Marika Piciocchi , Alessandro Sinigaglia , Enrico Lavezzo , Marina Bortolami , Andromachi Kotsafti , Umberto Cillo , Giacomo Zanus , Claudia Mescoli , Massimo Rugge , Fabio Farinati
Published: May 2012

Background

MicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS), host’s repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG) in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the expression of several microRNAs, non-coding genes involved in post-transcriptional regulation, cell proliferation, differentiation and death.

Methods

Tissue samples obtained either at surgery, [neoplastic (HCC) and adjacent non-cancerous cirrhotic tissues (NCCT)] at percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis or patients undergoing cholecystectomy) were analysed for 8-OHdG (HPLC-ED), OGG1 (a DNA repair gene) polymorphism (PCR-RFLP), telomerase activity, telomere length (T/S, by RT-PCR), Taqman microRNA assay and Bad/Bax mRNA (RT-PCR). Fifty-eight samples from 29 HCC patients (obtained in both neoplastic and peritumoral tissues), 22 from chronic hepatitis (CH) and 10 controls (cholecystectomy patients - CON) were examined.

Results

Eight-OHdG levels were significantly higher in HCC and NCCT than in CH and CON (p=0.001). Telomerase activity was significantly higher in HCC than in the remaining subgroups (p=0.002); conversely T/S was significantly lower in HCC (p=0.05). MiR-199a-b, -195, -122, -92a and −145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A positive correlation was observed among 8-OHdG levels, disease stage, telomerase activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA.

Conclusions

The above findings confirm the accumulation, in the progression of chronic liver damage to HCC, of a ROS-mediated oxidative DNA damage, and suggest that this correlates with induction of telomerase activity and, as a novel finding, with over-expression of miR-92, a microRNA that plays a role in both the apoptotic process and in cellular proliferation pathways.
Retro-mode imaging and fundus autofluorescence with scanning laser ophthalmoscope of retinal dystrophies
Authors: Maurizio Battaglia Parodi , Pierluigi Iacono , Stelios Kontadakis , Stefano Vergallo , Marialucia Cascavilla , Ilaria Zucchiatti , Francesco Bandello
Published: May 2012

Background

Retinal dystrophies display a considerably wide range of phenotypic variability, which can make diagnosis and clinical staging difficult. The aim of the study is to analyze the contribution of retro-mode imaging (RMI) and fundus autofluorescence (FAF) to the characterization of retinal dystrophies.

Methods

Eighteen consecutive patients affected by retinal dystrophies underwent a complete ophthalmological examination, including best corrected visual acuity with ETDRS charts, blue-light fundus autofluorescence, (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), and RMI. The primary outcome was the identification of abnormal patterns on RMI. The secondary outcome was the correlation with the findings on BL-FAF and NIR-FAF.

Results

Overall, the main feature of RMI is represented by a pseudo-3D pattern of all the lesions at the posterior pole. More specifically, any accumulation of material within the retina appears as an area of elevation of different shape and size, displaying irregular and darker borders. No precise correlations between RMI, BL-AF, and NIR-AF imaging was found.

Conclusions

RMI and FAF appear to be useful tools for characterizing retinal dystrophies. Non-invasive diagnostic tools may yield additional information on the clinical setting and the monitoring of the patients.
Experience with using second life for medical education in a family and community medicine education unit
Authors: Melús-Palazón Elena , Bartolomé-Moreno Cruz , Palacín-Arbués Juan Carlos , Lafuente-Lafuente Antonio , García Inmaculada García , Guillen Sara , Esteban Ana B , Clemente Silvia , Marco Ángeles M , Gargallo Pilar M , López Carlos , Magallón-Botaya Rosa
Published: May 2012

Background

The application of new technologies to the education of health professionals is both a challenge and a necessity. Virtual worlds are increasingly being explored as a support for education. Aim: The aim of this work is to study the suitability of Second Life (SL) as an educational tool for primary healthcare professionals.

Methods

Design: Qualitative study of accredited clinical sessions in SL included in a continuing professional development (CPD) programme for primary healthcare professionals. Location: Zaragoza I Zone Family and Community Medicine Education Unit (EU) and 9 health centres operated by the Aragonese Health Service, Aragon, Spain. Method: The EU held two training workshops in SL for 16 healthcare professionals from 9 health centres by means of two workshops, and requested them to facilitate clinical sessions in SL. Attendance was open to all personnel from the EU and the 9 health centres. After a trail period of clinical sessions held at 5 health centres between May and November 2010, the CPD-accredited clinical sessions were held at 9 health centres between February and April 2011. Participants: 76 healthcare professionals attended the CPD-accredited clinical sessions in SL. Main measurements: Questionnaire on completion of the clinical sessions.

Results

Response rate: 42-100%. Questionnaire completed by each health centre on completion of the CPD-accredited clinical sessions: Access to SL: 2 centres were unable to gain access. Sound problems: 0% (0/9). Image problems: 0% (0/9). Voice/text chat: used in 100% (10/9); 0 incidents. Questionnaire completed by participants in the CPD-accredited clinical sessions: Preference for SL as a tool: 100% (76/76). Strengths of this method: 74% (56/76) considered it eliminated the need to travel; 68% (52/76) believed it made more effective use of educational resources; and 47% (36/76) considered it improved accessibility. Weaknesses: 91% (69/76) experienced technical problems, while; 9% (7/76) thought it was impersonal and with little interaction. 65.79% (50/76) believed it was better than other distance learning methods and 38.16% (29/76) believed it was better than face-to-face learning.

Conclusions

SL is a tool that allows educational activities to be designed that involve a number of health centres in different geographical locations, consequently eliminating the need to travel and making more effective use of educational resources.
High-density lipoprotein subclass and particle size in coronary heart disease patients with or without diabetes
Authors: Tian Li , Long Shiyin , Li Chuanwei , Liu Yinghui , Chen Yucheng , Zeng Zhi , Fu Mingde
Published: May 2012

Background

A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes.

Methods

Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection.

Results

Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+preβ2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The preβ1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+preβ2.

Conclusions

The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.
Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease
Authors: Gao Wei , He Hui-Wei , Wang Ze-Mu , Zhao Huan , Lian Xiao-Qing , Wang Yong-Sheng , Zhu Jun , Yan Jian-Jun , Zhang Ding-Guo , Yang Zhi-Jian , Wang Lian-Sheng
Published: May 2012

Background

Hyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia.

Methods

In the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance.

Results

Our results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma.

Conclusions

Our results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.
Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery
Authors: Hoffmeister Cristiane RD , Durli Taís L , Schaffazick Scheila R , Raffin Renata P , Bender Eduardo A , Beck Ruy CR , Pohlmann Adriana R , Guterres Sílvia S
Published: May 2012

The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% (w/v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.
Novel regulatory therapies for prevention of Graft-versus-host disease
Authors: Leventhal Joseph , Huang Yiming , Xu Hong , Goode Idona , Ildstad Suzanne T
Published: May 2012

Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease.
Impact of patient-prosthesis mismatch on 30-day outcomes in young and middle-aged patients undergoing aortic valve replacement
Authors: Hernández-Vaquero Daniel , Llosa Juan C , Díaz Rocío , Khalpey Zain , Morales Carlos , Álvarez Rubén , López Jose , Boye Francisco
Published: May 2012

Background

The impact of patient-prosthesis mismatch (PPM) on early outcomes in young and middle-aged patients undergoing conventional aortic valve replacement for severe aortic stenosis remains unknown. Our objective was to evaluate the incidence of some degree of PPM and its influence on early mortality and morbidity.

Methods

We analyzed our single center experience in all patients <70 years undergoing first-time isolated aortic valve replacement for severe stenosis in our center from September 2007 to September 2011. PPM was defined as an indexed effective orifice area ≤ 0,85 cm2/m2. The influence of PPM on early mortality and postoperative complications was studied using propensity score analysis. Follow up at 30 postoperative days was 100% complete.

Results

Of 199 patients studied, 61 (30,7%) had some degree of PPM. PPM was associated with an increased postoperative mortality (OR = 8,71; 95% CI = 1,67–45,29; p = 0,04) and major postoperative complications (OR = 2,96; CI = 1,03–8,55; p = 0,044). However, no association between PPM and prolonged hospital or ICU stay was demonstrated.

Conclusions

Moderate PPM is a common finding in young and middle-aged patients undergoing surgery for aortic valve replacement due to severe stenosis. In addition, its influence on early outcomes may be relevant.
Outlier Detection using Projection Quantile Regression for Mass Spectrometry Data with Low Replication
Authors: Eo Soo-Heang , Pak Daewoo , Choi Jeea , Cho HyungJun
Published: May 2012

Background

Mass spectrometry (MS) data are often generated from various biological or chemical experiments and there may exist outlying observations, which are extreme due to technical reasons. The determination of outlying observations is important in the analysis of replicated MS data because elaborate pre-processing is essential for successful analysis with reliable results and manual outlier detection as one of pre-processing steps is time-consuming. The heterogeneity of variability and low replication are often obstacles to successful analysis, including outlier detection. Existing approaches, which assume constant variability, can generate many false positives (outliers) and/or false negatives (non-outliers). Thus, a more powerful and accurate approach is needed to account for the heterogeneity of variability and low replication.

Findings

We proposed an outlier detection algorithm using projection and quantile regression in MS data from multiple experiments. The performance of the algorithm and program was demonstrated by using both simulated and real-life data. The projection approach with linear, nonlinear, or nonparametric quantile regression was appropriate in heterogeneous high-throughput data with low replication.

Conclusion

Various quantile regression approaches combined with projection were proposed for detecting outliers. The choice among linear, nonlinear, and nonparametric regressions is dependent on the degree of heterogeneity of the data. The proposed approach was illustrated with MS data with two or more replicates.
Early course of microcirculatory perfusion in eye and digestive tract during hypodynamic sepsis
Authors: Pranskunas Andrius , Pilvinis Vidas , Dambrauskas Zilvinas , Rasimaviciute Renata , Planciuniene Rita , Dobozinskas Paulius , Veikutis Vincentas , Vaitkaitis Dinas , Boerma E Christiaan
Published: May 2012

Introduction

The aim of the study was to evaluate and compare the microcirculatory perfusion during experimental sepsis in different potentially available parts of the body, such as sublingual mucosa, conjunctiva of the eye, and mucosa of jejunum and rectum.

Methods

Pigs were randomly assigned to sepsis (n = 9) and sham (n = 4) groups. The sepsis group received a fixed dose of live Escherichia coli infusion over a 1-hour period (1.8 × 109/kg colony-forming units). Animals were observed 5 hours after the start of E. coli infusion. In addition to systemic hemodynamic assessment, we performed conjunctival, sublingual, jejunal, and rectal evaluation of microcirculation by using Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline, and at 3 and 5 hours after the start of live E. coli infusion. Assessment of microcirculatory parameters of convective oxygen transport (microvascular flow index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance (perfused vessel density (PVD) and total vessel density (TVD)) was done by using a semiquantitative method.

Results

Infusion of E. coli resulted in a hypodynamic state of sepsis associated with low cardiac output and increased systemic vascular resistance despite fluid administration. Significant decreases in MFI and PPV of small vessels were observed in sublingual, conjunctival, jejunal, and rectal locations 3 and 5 hours after the start of E. coli infusion in comparison with baseline variables. Correlation between sublingual and conjunctival (r = 0.80; P = 0.036), sublingual and jejunal (r = 0.80; P = 0.044), and sublingual and rectal (r = 0.79; P = 0.03) MFI was observed 3 hours after onset of sepsis. However, this strong correlation between the sublingual and other regions disappeared 5 hours after the start of E. coli infusion. Overall, the sublingual mucosa exhibited the most-pronounced alterations of microcirculatory flow in comparison with conjunctival, jejunal, and rectal microvasculature (P < 0.05).

Conclusions

In this pig model, a time-dependent correlation exists between sublingual and microvascular beds during the course of a hypodynamic state of sepsis.
Early acute kidney injury and sepsis: a multicentre evaluation
Authors: Bagshaw Sean M , George Carol , Bellomo Rinaldo ,   the ANZICS Database Management Committee
Published: May 2012

Introduction

We conducted a study to evaluate the incidence, risk factors and outcomes associated with early acute kidney injury (AKI) in sepsis.

Methods

The study was a retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were collected from 57 intensive care units (ICUs) across Australia. In total, 120,123 patients admitted to ICU for more than 24 hours from 1 January 2000 to 31 December 2005 were included in the analysis. The main outcome measures were clinical and laboratory data and outcomes.

Results

Of 120,123 patients admitted, 33,375 had a sepsis-related diagnosis (27.8%). Among septic patients, 14,039 (42.1%) had concomitant AKI (septic AKI). Sepsis accounted for 32.4% of all patients with AKI. For septic AKI stratified by RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease) category, 38.5% of patients belonged to the risk category, 38.8% to the injury category and 22.7% to the failure category. Septic AKI patients had greater acuity of illness (P < 0.0001), lower blood pressure (P < 0.0001), higher heart rates (P < 0.0001), worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio (P < 0.0001), greater acidaemia (P < 0.0001) and higher white cell counts (P < 0.0001) compared with patients with nonseptic AKI. Septic AKI was also associated with greater severity of AKI (RIFLE category injury or failure) compared with nonseptic AKI. Septic AKI was associated with a significantly higher crude and co-variate adjusted mortality in the ICU (19.8% versus 13.4%; odds ratio 1.60, 95% confidence interval 1.5 to 1.7; P < 0.001) and in hospital (29.7% versus 21.6%; odds ratio 1.53, 95% confidence interval 1.46 to 1.60; P < 0.001) compared with nonseptic AKI. Septic AKI was associated with higher ICU and hospital mortality across all strata of RIFLE categories. Septic AKI patients had longer durations of stay in both ICU and hospital across all strata of RIFLE categories.

Conclusion

Septic AKI is common during the first 24 hours after ICU admission. Patients with septic AKI are generally sicker, with a higher burden of illness, and have greater abnormalities in acute physiology compared with patients with nonseptic AKI. Moreover, septic AKI is independently associated with higher odds of death and longer duration of hospitalization.
Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation
Authors: Garderet Laurent , Iacobelli Simona , Moreau Philippe , Dib Mamoun , Lafon Ingrid , Niederwieser Dietger , Masszi Tamas , Fontan Jean , Michallet Mauricette , Gratwohl Alois , Milone Giuseppe , Doyen Chantal , Pegourie Brigitte , Hajek Roman , Casassus Philippe , Kolb Brigitte , Chaleteix Carine , Hertenstein Bernd , Onida Francesco , Ludwig Heinz , Ketterer Nicolas , Koenecke Christian , van Os Marleen , Mohty Mohamad , Cakana Andrew , Gorin Norbert Claude , de Witte Theo , Harousseau Jean Luc , Morris Curly , Gahrton Gösta
Published: May 2012

Purpose

This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT).

Patients and Methods

Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months).

Results

Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P = .001), and the median duration of response was longer (17.9 v 13.4 months; P = .04). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia.

Conclusion

VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.
Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial
Authors: Faderl Stefan , Wetzler Meir , Rizzieri David , Schiller Gary , Jagasia Madan , Stuart Robert , Ganguly Siddhartha , Avigan David , Craig Michael , Collins Robert , Maris Michael , Kovacsovics Tibor , Goldberg Stuart , Seiter Karen , Hari Parameswaran , Greiner Jochen , Vey Norbert , Recher Christian , Ravandi Farhad , Wang Eunice S. , Vasconcelles Michael , Huebner Dirk , Kantarjian Hagop M.
Published: May 2012

Purpose

To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML).

Patients and Methods

Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m2 or a placebo followed by Ara-C 1 g/m2 for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety.

Results

Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively).

Conclusion

Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.
Resveratrol Stimulates Cortisol Biosynthesis by Activating SIRT-Dependent Deacetylation of P450scc
Authors: Li Donghui , Dammer Eric B. , Sewer Marion B.
Published: May 2012

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450.