bluuebunny/crossref_metadata_2025 huggingface dataset:
A camera as a sensor for lighting and shading control
Authors: Newsham GR , Arsenault C.
Published: May 2009

We developed a proof-of-concept prototype camera-based system for lighting and shading control. The system utilised a simple CMOS-based digital camera with an approximate v-lambda filter, calibrated to provide pixel luminance values up to 10,000 cd/m 2. We demonstrated that the single camera sensor has the potential to replace the multiple sensors required by conventional systems for daylight harvesting, shading control and occupancy sensing. Performance similar to conventional systems was replicated, but in addition, alternate control algorithms based on spatial luminance information were demonstrated. However, considerable further development would be required to produce a commercial version, and there may be resistance to deployment due to privacy issues. Cameras offer other potential valuable end uses, examples are fire detection and security, which could effectively subsidise the lighting control functions, making automatic lighting controls more financially attractive, and promoting energy savings.
The utility of the Necessity—Concerns Framework in explaining treatment non-adherence in four chronic illness groups in Italy
Authors: Tibaldi Giuseppe , Clatworthy Jane , Torchio Elisabetta , Argentero Piergiorgio , Munizza Carmine , Horne Rob
Published: May 2009

Objective: To translate the Beliefs about Medicines Questionnaire (BMQ) into Italian and explore the utility of the Necessity—Concerns Framework in explaining treatment non-adherence in four chronic illness groups in Italy.

Methods: 449 patients with chronic illness (depression, asthma, diabetes and cardiac disease) were approached at outpatient clinics in Turin and asked to complete Italian translations of the BMQ and the Medication Adherence Report Scale.

Results: 427 patients consented to participate in the study. The BMQ demonstrated good internal consistency, with Cronbach's alphas of 0.78 (Necessity subscale) and 0.72 (Concerns subscale). Participants were divided into four attitudinal groups based on their responses to the BMQ: 59% Accepting (high Necessity, low Concerns), 29% ambivalent (high Necessity, high Concerns), 8% Indifferent (low Necessity, low Concerns) and 4% Skeptical (low Necessity, high Concerns). Those in the Accepting group reported the highest adherence to medication and those in the Skeptical group the lowest (p50.01).

Discussion: The BMQ has been successfully translated and validated in Italian. This study provides support for the Necessity—Concerns Framework in explaining medication non-adherence in chronic illness. Interventions that address low perceived need for treatment and concerns about potential adverse effects of treatment are likely to facilitate optimal use of medicines.
Will healthcare reform actually occur in the US?
Authors: Creer Thomas L.
Published: May 2009

Healthcare in the US is currently in a state of chaos. Not only does a large percentage of the population lack health coverage, but overall we are increasingly paying more and more for what in comparison to other countries is a decreasing quality of healthcare. This article describes a few of the factors that compose the context both of current healthcare strategies in the US and of barriers to the creation of a true healthcare system. Accomplishing this goal will require unprecedented bipartisan cooperation of both the Obama administration and Congress.
Activation of peroxisome proliferator-activated receptor-γ potentiates pro-inflammatory cytokine production, and adrenal and somatotropic changes of weaned pigs after Escherichia coli lipopolysaccharide challenge
Authors: Yulan Liu  , Junxia Shi  , Jing Lu  , Guoquan Meng  , Huiling Zhu  , Yongqing Hou  , Yulong Yin  , Shengjun Zhao  , Binying Ding
Published: May 2009

Our previous study demonstrated mRNA and protein expression of peroxisome proliferator-activated receptor-g (PPAR-g) in the immune system of weaned pigs. In this report, to test the hypothesis that activation of PPAR-g in immune system modulates inflammatory response, and adrenal and somatotropic responses associated with immune challenge, we administered intraperitoneally PPAR-g agonist and/or antagonist in weaned pigs subjected to Escherichia coli lipopolysaccharide (LPS) challenge. Unexpectedly, we found that a single injection of the PPAR-g agonist rosiglitazone (given at 3 mg/kg body weight 30 min before LPS injection) failed to block pro-inflammatory cytokine production induced by LPS injection. Rather, plasma levels of tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6), mRNA abundance of TNF-a in thymus, spleen, mesenteric lymph node and peripheral white blood cells, mRNA abundance of IL-6 in thymus, protein levels of TNF-a in spleen and mesenteric lymph node, and protein levels of IL-6 in spleen and mesenteric lymph node, were elevated beyond the levels in control pigs injected with LPS. Furthermore, rosiglitazone potentiated the increase of plasma cortisol and prostaglandin E2 concentrations, and the decrease of plasma insulin-like growth factor-1 concentration induced by LPS injection. Co-administration of the PPAR-g antagonist bisphenol A diglycidyl ether (given 30 mg/kg body weight) 30 min prior to treatment with rosiglitazone antagonized the effect of the PPAR-g agonist, indicating a PPAR-g-dependent effect. Our data indicate that ligand-induced activation of PPAR-g does not ameliorate but enhances pro-inflammatory cytokine production, and further potentiates the adrenal and somatotropic changes in weaned pigs subjected to E. coli LPS challenge, which suggests that PPAR-g activation may not be useful, but potentially harmful, in the treatment of immune challenge in livestock. Our results raise doubts about the prevalently accepted anti-inflammatory role for PPAR-g activation.
The comparison of early and late outcome of direct and conventional stenting of patients with st elevation myocardial infarction
Authors: Tacoy Gulten , Yazici Guliz Erdem , Erden Murat , Timurkaynak Timur
Published: May 2009

Background: The aim of this study was to compare direct and conventional stenting procedure in the subacute stable phase on short- and long-term results in patients with ST elevation myocardial infarction.

Methods: Eighty-eight clinically stable ST-segment elevation myocardial infarction (STEMI) patients were enrolled into the study. The patients were classified as group I (direct stenting) and group II (conventional stenting — stenting after balloon dilatation). Baseline characteristics of patients were scanned from hospital records. Coronary angiograms before and after the revascularization procedure were evaluated with the quantitative coronary angiogram technique. Patients were followed for 5 years for clinical outcomes. The study population consisted of 58 patients (65%) in group I and 30 patients (35%) in group II. Mean ages were 55.8 ± 10.8 and 57.3 ± 9.8, respectively.

Results: There were no significant differences between the two groups regarding clinical characteristics (hypertension, diabetes mellitus, family history of cardiovascular disease, smoking and dyslipidemia). The thrombus score was similar in both groups. Diameter stenosis was lower in group I (54.8 ± 12.7 versus 61.4 ± 12.6; p = 0.023) and TFC (Thrombolysis in Myocardial Infarction frame count) was higher in group II (30.7 ± 14.5 versus 40.8 ± 26.7; p = 0.02) before the percutaneous coronary intervention (PCI). Other quantitative angiographic parameters were not different. For all angiographic criteria, the difference between pre- and post-PCI parameters was significantly different in both groups. However, the change in TFC was higher within the group II compared to pre-PCI TFC rates. This difference was statistically significant ( p = 0.002). Procedural success was statistically different between groups (69% in group I, 43% in group II; p50.01). Immediate clinical and angiographic results were similar. At 5-year follow-up the incidence of major adverse cardiac events including death, angina pectoris and myocardial infarction were similar for direct stenting versus conventional angioplasty.

Conclusions: Direct stenting is safe and feasible for the treatment in patients with STEMI at the subacute phase. Immediate clinic, angiographic and late clinical results are similar for direct stenting and conventional stenting following balloon angioplasty. Although conventional stenting improved TFC better than direct stenting, this did not translate to better clinical outcomes.
Indoleamine 2,3-dioxygenase–expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells
Authors: Chung David J. , Rossi Marco , Romano Emanuela , Ghith Jennifer , Yuan Jianda , Munn David H. , Young James W.
Published: May 2009

A comprehensive understanding of the complex, autologous cellular interactions and regulatory mechanisms that occur during normal dendritic cell (DC)–stimulated immune responses is critical to optimizing DC-based immunotherapy. We have found that mature, immunogenic human monocyte-derived DCs (moDCs) up-regulate the immune-inhibitory enzyme, indoleamine 2,3-dioxygenase (IDO). Under stringent autologous culture conditions without exogenous cytokines, mature moDCs expand regulatory T cells (Tregs) by an IDO-dependent mechanism. The priming of resting T cells with autologous, IDO-expressing, mature moDCs results in up to 10-fold expansion of CD4+CD25brightFoxp3+CD127neg Tregs. Treg expansion requires moDC contact, CD80/CD86 ligation, and endogenous interleukin-2. Cytofluorographically sorted CD4+ CD25brightFoxp3+ Tregs inhibit as much as 80% to 90% of DC-stimulated autologous and allogeneic T-cell proliferation, in a dose-dependent manner at Treg:T-cell ratios of 1:1, 1:5, and as low as 1:25. CD4+CD25brightFoxp3+ Tregs also suppress the generation of cytotoxic T lymphocytes specific for the Wilms tumor antigen 1, resulting in more than an 80% decrease in specific target cell lysis. Suppression by Tregs is both contact-dependent and transforming growth factor-β–mediated. Although mature moDCs can generate Tregs by this IDO-dependent mechanism to limit otherwise unrestrained immune responses, inhibition of this counter-regulatory pathway should also prove useful in sustaining responses stimulated by DC-based immunotherapy.
CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells
Authors: Del Cornò Manuela , Michienzi Alessandro , Masotti Andrea , Da Sacco Letizia , Bottazzo Gian Franco , Belardelli Filippo , Gessani Sandra
Published: May 2009

Toll-like receptor (TLR) signaling activation by pathogens is critical to the induction of immune responses, and demands tight regulation. We describe in this study that CC chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (DCs). Impaired CCL2 secretion occurs concomitantly to interleukin-12 up-regulation, being part of a complex regulatory circuit ensuring optimal T helper type 1 polarization. Interestingly, triggering selected TLRs or their combinations differently affects nuclear factor-κB p65 activation and microRNA expression. Overall, these results indicate that CCL2 supplies an important immunomodulatory role to DCs, and may contribute to dictate the cytokine profile in T helper type 1 responses induced by DCs.
HBV replication is significantly reduced by IL-6
Authors: Kuo Tzer-Min , Hu Cheng-po , Chen Ya-Ling , Hong Ming-Hsiang , Jeng King-Song , Liang Chun-Chin T , Chen Mong-Liang , Chang Chungming
Published: May 2009

Interleukin-6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV) replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA) in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.
IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico
Authors: Wu Tzong-Yuan , Hsieh Chi-Chun , Hong Jun-Jie , Chen Chung-Yung , Tsai Yuh-Show
Published: May 2009

Background

Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements.

Results

We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.

Conclusion

IRSS is freely available at this website http://140.135.61.9/ires/. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.
Genetic analysis of an F2 intercross between two chicken lines divergently selected for body-weight
Authors: Wahlberg Per , Carlborg Örjan , Foglio Mario , Tordoir Xavier , Syvänen Ann-Christine , Lathrop Mark , Gut Ivo G , Siegel Paul B , Andersson Leif
Published: May 2009

Background

We have performed Quantitative Trait Loci (QTL) analysis of an F2 intercross between two chicken lines divergently selected for juvenile body-weight. In a previous study 13 identified loci with effects on body-weight, only explained a small proportion of the large variation in the F2 population. Epistatic interaction analysis however, indicated that a network of interacting loci with large effect contributed to the difference in body-weight of the parental lines. This previous analysis was, however, based on a sparse microsatellite linkage map and the limited coverage could have affected the main conclusions. Here we present a revised QTL analysis based on a high-density linkage map that provided a more complete coverage of the chicken genome. Furthermore, we utilized genotype data from ~13,000 SNPs to search the genome for potential selective sweeps that have occurred in the selected lines.

Results

We constructed a linkage map comprising 434 genetic markers, covering 31 chromosomes but leaving seven microchromosomes uncovered. The analysis showed that seven regions harbor QTL that influence growth. The pair-wise interaction analysis identified 15 unique QTL pairs and notable is that nine of those involved interactions with a locus on chromosome 7, forming a network of interacting loci. The analysis of ~13,000 SNPs showed that a substantial proportion of the genetic variation present in the founder population has been lost in either of the two selected lines since ~60% of the SNPs polymorphic among lines showed fixation in one of the lines. With the current marker coverage and QTL map resolution we did not observe clear signs of selective sweeps within QTL intervals.

Conclusion

The results from the QTL analysis using the new improved linkage map are to a large extent in concordance with our previous analysis of this pedigree. The difference in body-weight between the parental chicken lines is caused by many QTL each with a small individual effect. Although the increased chromosomal marker coverage did not lead to the identification of additional QTL, we were able to refine the localization of QTL. The importance of epistatic interaction as a mechanism contributing significantly to the remarkable selection response was further strengthened because additional pairs of interacting loci were detected with the improved map.
Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat
Authors: Sivilia Sandra , Giuliani Alessandro , Fernández Mercedes , Turba Maria Elena , Forni Monica , Massella Alessandro , De Sordi Nadia , Giardino Luciana , Calzà Laura
Published: May 2009

Background

The neurotrophin nerve growth factor (NGF) is produced by different cell types in the anterior and posterior eye, exerting a neuroprotective role in the adult life. The visual system is highly sensitive to NGF and the retina and optic nerve provides suitable subjects for the study of central nervous system degeneration. The model of bilateral carotid occlusion (two-vessel occlusion, 2VO) is a well-established model for chronic brain hypoperfusion leading to brain capillary pathology, to retina and optic nerve degeneration. In order to study if a single intravitreal injection of NGF protects the retina and the optic nerve from degeneration during systemic circulatory diseases, we investigated morphological and molecular changes occurring in the retina and optic nerve of adult rats at different time-points (8, 30 and 75 days) after bilateral carotid occlusion.

Results

We demonstrated that a single intravitreal injection of NGF (5 μg/3 μl performed 24 hours after 2VO ligation) has a long-lasting protective effect on retina and optic nerve degeneration. NGF counteracts retinal ganglion cells degeneration by early affecting Bax/Bcl-2 balance- and c-jun- expression (at 8 days after 2VO). A single intravitreal NGF injection regulates the demyelination/remyelination balance after ischemic injury in the optic nerve toward remyelination (at 75 days after 2VO), as indicated by the MBP expression regulation, thus preventing optic nerve atrophy and ganglion cells degeneration. At 8 days, NGF does not modify 2VO-induced alteration in VEFG and related receptors mRNA expression.

Conclusion

The protective effect of exogenous NGF during this systemic circulatory disease seems to occur also by strengthening the effect of endogenous NGF, the synthesis of which is increased by vascular defect and also by the mechanical lesion associated with NGF or even vehicle intraocular delivery.
Elevated HIV risk behaviour among recently incarcerated injection drug users in a Canadian setting: a longitudinal analysis
Authors: Milloy M-J S , Buxton Jane , Wood Evan , Li Kathy , Montaner Julio SG , Kerr Thomas
Published: May 2009

Background

While incarceration has consistently been associated with a higher risk of HIV infection for individuals who use injection drugs (IDU), the effect of incarceration on the post-release risk environment remains poorly described. We sought to assess the impact of incarceration on risk factors for HIV infection after release from prison in a sample of active IDU in Vancouver, Canada.

Methods

Using a prospective cohort of community-recruited IDU followed from May 1, 1996 to November 30, 2005, we examined contingency tables and performed linear growth curve analyses to assess changes in the prevalence of independent risk factors for HIV infection from before to after a period of incarceration among participants reporting incarceration and a matched control group.

Results

Of the 1603 participants followed-up over the study period, 147 (9.2%) were eligible for an analysis of post-incarceration risk behaviours and 742 (46.3%) were used as matched controls. Significant differences were found in one or both groups for the prevalence of frequent cocaine injection, requiring help injecting, binge drug use, residence in the HIV outbreak epicentre, sex-trade participation and syringe sharing (all p < 0.05) after incarceration. In linear growth curve adjusted for age, gender and ethnicity, syringe sharing was significantly more common in those recently released from prison (p = 0.03) than in the control group.

Conclusion

In a sample of Canadian IDU, we did not observe any effect of incarceration on the prevalence of several behaviours that are risk factors for HIV infection, including intensity of drug use or participation in the sex trade. However, those recently released from prison were more likely to report syringe sharing that those in a matched control group.
The management of neuropathic ulcers of the foot in diabetes by shock wave therapy
Authors: Moretti Biagio , Notarnicola Angela , Maggio Giulio , Moretti Lorenzo , Pascone Michele , Tafuri Silvio , Patella Vittorio
Published: May 2009

Background

Diabetes is becoming one of the most common chronic diseases, and ulcers are its most serious complication. Beginning with neuropathy, the subsequent foot wounds frequently lead to lower extremity amputation, even in the absence of critical limb ischemia. In recent years, some researchers have studied external shock wave therapy (ESWT) as a new approach to soft tissue wound healing. The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers.

Methods

We designed a randomized, prospective, controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies. One group was treated with standard care and shock wave therapy. The other group was treated with only standard care. The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization.

Results

After 20 weeks of treatment, 53.33% of the ESWT-treated patients had complete wound closure compared with 33.33% of the control patients, and the healing times were 60.8 and 82.2 days, respectively (p < 0.001). Significant differences in the index of the re-epithelization were observed between the two groups, with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group (p < 0.001).

Conclusion

Therefore, ESWT may be a useful adjunct in the management of diabetic foot ulceration.

Trial registration

Current Controlled Trials ISRCTN21800909
State diagrams of the heart – a new approach to describing cardiac mechanics
Authors: Larsson Matilda , Bjällmark Anna , Johnson Jonas , Winter Reidar , Brodin Lars-Åke , Lundbäck Stig
Published: May 2009

Background

Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements.

Methods

We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter- and intraventricular function of the heart by displaying the cardiac phases.

Results

The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods.

Conclusion

The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.
Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus
Authors: Deren Kelley E , Forsyth Jennifer , Abdullah Osama , Hsu Edward W , Klinge Petra M , Silverberg Gerald D , Johanson Conrad E , McAllister James P
Published: May 2009

Background

Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus.

Methods

Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP.

Results

When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP.

Conclusion

Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.
Over 50 years of trial in Acta Psychiatrica Scandinavica: a survey
Authors: Matar Hosam E , Almerie Muhammad Q , Al Marhi Muhammad O , Adams Clive E
Published: May 2009

Background

Randomised controlled trials are the gold standard for evaluating mental health care interventions. We assessed the content and quality of trials published in Acta Psychiatrica Scandinavica and Supplementum since 1948.

Methods

All trials were identified manually, quality assessed, data extracted, and sought on Medline.

Results

About 8.6% of all reports in the journal were clinical trials (n = 582) with the peak frequency in the 1980s. Most originate from Europe (80%) and focus on depression (~38%) or schizophrenia (27%). The median sample size is 44. We found only two trials that fully met the criteria of quality reporting RCTs set by CONSORT statements (0.34%) since 1996. Less than 50% of records were possible to identify by a Medline search using broad methodological terms.

Conclusion

Acta is a major source of health trials. The standard of reporting is similar to other journals but better adherence to CONSORT would ensure higher quality of reports and better dissemination.
Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer
Authors: Katargin Alexey N , Pavlova Larissa S , Kisseljov Fjodor L , Kisseljova Natalia P
Published: May 2009

Background

Large-scale screening methods are widely used to reveal cancer-specific DNA methylation markers. We previously identified non-satellite 3.3-kb repeats associated with facioscapulohumeral muscular dystrophy (FSHD) as hypermethylated in cervical cancer in genome-wide screening. To determine whether hypermethylation of 3.3-kb repeats is a tumor-specific event and to evaluate frequency of this event in tumors, we investigated the 3.3-kb repeat methylation status in human papilloma virus (HPV)-positive cervical tumors, cancer cell lines, and normal cervical tissues. Open reading frames encoding DUX family proteins are contained within some 3.3-kb repeat units. TheDUXmRNA expression profile was also studied in these tissues.

Methods

The methylation status of 3.3-kb repeats was evaluated by Southern blot hybridization and bisulfite genomic sequencing. The expression ofDUXmRNA was analyzed by RT-PCR and specificity of PCR products was confirmed by sequencing analysis.

Results

Hypermethylation of 3.3-kb repeats relative to normal tissues was revealed for the first time in more than 50% (18/34) of cervical tumors and in 4 HPV-positive cervical cancer cell lines. Hypermethylation of 3.3-kb repeats was observed in tumors concurrently with or independently of hypomethylation of classical satellite 2 sequences (Sat2) that were hypomethylated in 75% (15/20) of cervical tumors. We have revealed the presence of transcripts highly homologous toDUX4andDUX10genes in normal tissues and down-regulation of transcripts in 68% of tumors with and without 3.3-kb repeats hypermethylation.

Conclusion

Our results demonstrate that hypermethylation rather than hypomethylation of 3.3-kb repeats is the predominant event in HPV-associated cervical cancer and provide new insight into the epigenetic changes of repetitive DNA elements in carcinogenesis.
Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients
Authors: Richiardi Lorenzo , Fiano Valentina , Vizzini Loredana , De Marco Laura , Delsedime Luisa , Akre Olof , Tos Anna Gillio , Merletti Franco
Published: May 2009

Purpose

There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients.

Methods

We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3).

Results

The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer–specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort.

Conclusion

The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.
MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02
Authors: Khor Li-Yan , Bae Kyounghwa , Paulus Rebecca , Al-Saleem Tahseen , Hammond M. Elizabeth , Grignon David J. , Che Mingxin , Venkatesan Varagur , Byhardt Roger W. , Rotman Marvin , Hanks Gerald E. , Sandler Howard M. , Pollack Alan
Published: May 2009

Purpose

MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02.

Patients and Methods

Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM).

Results

In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM).

Conclusion

Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.
Conversion to Resectability Using Hepatic Artery Infusion Plus Systemic Chemotherapy for the Treatment of Unresectable Liver Metastases From Colorectal Carcinoma
Authors: Kemeny Nancy E. , Melendez Fidel D. Huitzil , Capanu Marinela , Paty Philip B. , Fong Yuman , Schwartz Lawrence H. , Jarnagin William R. , Patel Dina , D'Angelica Michael
Published: May 2009

Purpose

To determine the conversion to resectability in patients with unresectable liver metastases from colorectal cancer treated with hepatic arterial infusion (HAI) plus systemic oxaliplatin and irinotecan (CPT-11).

Patients and Methods

Forty-nine patients with unresectable liver metastases (53% previously treated with chemotherapy) were enrolled onto a phase I protocol with HAI floxuridine and dexamethasone plus systemic chemotherapy with oxaliplatin and irinotecan.

Results

Ninety-two percent of the 49 patients had complete (8%) or partial (84%) response, and 23 (47%) of the 49 patients were able to undergo resection in a group of patients with extensive disease (73% with > five liver lesions, 98% with bilobar disease, 86% with ≥ six segments involved). For chemotherapy-naïve and previously treated patients, the median survival from the start of HAI therapy was 50.8 and 35 months, respectively. The only baseline variable significantly associated with a higher resection rate was female sex. Variables reflecting extensive anatomic disease, such as number of lesions or number of vessels involved, were not significantly associated with the probability of resection.

Conclusion

The combination of regional HAI floxuridine/dexamethasone and systemic oxaliplatin and irinotecan is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, demonstrating a 47% conversion to resection (57% in chemotherapy-naïve patients). Future randomized trials should compare HAI plus systemic chemotherapy with systemic therapy alone to assess the additional value of HAI therapy in converting patients with hepatic metastases to resectability.
American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk Reduction
Authors: Visvanathan Kala , Chlebowski Rowan T. , Hurley Patricia , Col Nananda F. , Ropka Mary , Collyar Deborah , Morrow Monica , Runowicz Carolyn , Pritchard Kathleen I. , Hagerty Karen , Arun Banu , Garber Judy , Vogel Victor G. , Wade James L. , Brown Powel , Cuzick Jack , Kramer Barnett S. , Lippman Scott M.
Published: May 2009

Purpose

To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction.

Methods

A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines.

Results

Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) –positive invasive tumors. Women ≤ 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality.

Recommendations

In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.
Cognitive Rehabilitation in Patients With Gliomas: A Randomized, Controlled Trial
Authors: Gehring Karin , Sitskoorn Margriet M. , Gundy Chad M. , Sikkes Sietske A.M. , Klein Martin , Postma Tjeerd J. , van den Bent Martin J. , Beute Guus N. , Enting Roelien H. , Kappelle Arnoud C. , Boogerd Willem , Veninga Theo , Twijnstra Albert , Boerman Dolf H. , Taphoorn Martin J.B. , Aaronson Neil K.
Published: May 2009

Purpose

Patients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas.

Patients and Methods

One hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health–related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up.

Results

At the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months.

Conclusion

The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.
Hospital Factors and Racial Disparities in Mortality After Surgery for Breast and Colon Cancer
Authors: Breslin Tara M. , Morris Arden M. , Gu Niya , Wong Sandra L. , Finlayson Emily V. , Banerjee Mousumi , Birkmeyer John D.
Published: May 2009

Purpose

Black patients have worse prognoses than whites with breast or colorectal cancer. Mechanisms underlying such disparities have not been fully explored. We examined the role of hospital factors in racial differences in late mortality after surgery for breast or colon cancer.

Methods

Patients undergoing surgery after new diagnosis of breast or colon cancer were identified using the Surveillance Epidemiology and End Results–Medicare linked database (1995 to 2005). The main outcome measure was mortality at 5 years. Proportional hazards models were used to assess relationships between race and late mortality, accounting for patient factors, socioeconomic measures, and hospital factors. Fixed and random effects models were used to account for quality differences across hospitals.

Results

Black patients, compared with white patients, had lower 5-year overall survival rates after surgery for breast (62.1% v 70.4%, respectively; P < .001) and colon cancer (41.3% v 45.4%, respectively; P < .001). After controlling for age, comorbidity, and stage, black race remained an independent predictor of mortality for breast (adjusted hazard ratio [HR] = 1.25; 95% CI, 1.16 to 1.34) and colon cancer (adjusted HR = 1.13; 95% CI, 1.07 to 1.19). After risk adjustment, hospital factors explained 36% and 54% of the excess mortality for black patients with breast cancer and colon cancer, respectively. Hospitals with large minority populations had higher late mortality rates independent of race.

Conclusion

Hospital factors, including quality, are important mediators of the association between race and mortality for breast and colon cancer. Hospital-level quality improvement should be a major component of efforts to reduce disparities in cancer outcomes.
The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects
Authors: Surya Sowmya , Horowitz Jeffrey F. , Goldenberg Naila , Sakharova Alla , Harber Matthew , Cornford Andrea S. , Symons Kathy , Barkan Ariel L.
Published: May 2009

Context: It is unclear whether the pattern of GH delivery to peripheral tissues has important effects.

Objective: The aim of the study was to compare the effects of pulsatile vs. continuous administration of GH upon metabolic and IGF-I parameters in obese subjects.

Setting: The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center.

Participants: Four men and five women with abdominal obesity (body mass index, 33 ± 3 kg/m2; body fat, 40 ± 3%) participated in the study.

Intervention: GH (0.5 mg/m2 · d) was given iv for 3 d as: 1) continuous infusion (C); and 2) pulsatile boluses (P) (15% of the dose at 0700, 1300, and 1800 h and 55% at 2400 h). These trials were preceded by a basal period (B) when subjects received normal saline.

Main Outcome Measures: Rate of lipolysis and hepatic glucose production were evaluated using stable isotope tracer techniques. The composite index of insulin sensitivity (Matsuda index) was assessed using oral glucose tolerance test.

Results: The increase in plasma IGF-I concentrations was greater (P < 0.05) with continuous GH infusion (211 ± 31, 423 ± 38, and 309 ± 34 μg/liter for B, C, and P, respectively). Muscle IGF-I mRNA was significantly increased (P < 0.05) only after the continuous GH infusion (1.2 ± 0.4, 4.4 ± 1.3, and 2.3 ± 0.6 arbitrary units, for B, C, and P, respectively). Only pulsatile GH augmented the rate of lipolysis (4.1 ± 0.3, 4.8 ± 0.7, and 7.1 ± 1.1 μmol/kg · min for B, C, and P, respectively). GH had no effect on hepatic glucose production, but both modes of GH administration were equally effective in impairing insulin sensitivity.

Conclusion: These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.
Dissecting the roles of Raf- and PI3K-signalling pathways in melanoma formation and progression in a zebrafish model
Authors: Michailidou Christina , Jones Mary , Walker Paul , Kamarashev Jivko , Kelly Amanda , Hurlstone Adam F. L.
Published: May 2009

Deregulated Ras signalling is implicated in most human neoplasia, exemplified by melanoma. Whereas Raf activation occurs almost ubiquitously in benign and malignant melanocytic neoplasms, implying an involvement in tumour initiation, phosphoinositide 3-kinase (PI3K) activation occurs predominantly in malignant neoplasms, implying an involvement in malignant progression. Here, we dissect the contributions of these two pathways to tumourigenesis in vivo, by modulating their activities in zebrafish melanocytes. Misexpression of oncogenic Ras (V12RAS) in founder fish induced frequent melanoma, beginning at larval stages, with concomitant activation of Raf-Mek-Erk and PI3K-Akt signalling. Misexpression of effector-domain mutants of V12RAS, or of various downstream effectors, confirmed a selective role for the Raf-Mek-Erk pathway in initiating neoplasia, but highlighted the requirement for additional Ras effector pathways for malignancy. The phenotype of animals with germ-line transmission of V12RAS resembled familial atypical mole and melanoma (FAMM) syndrome: melanocytes displayed hyperplasia, dysplasia, altered terminal differentiation and spontaneously progressed to invasive melanoma. Co-expressing a dominant-interfering form of PI3K abolished V12RAS-induced malignancy, demonstrating a direct role for PI3K signalling in the malignant progression of melanoma in vivo, and highlighting PI3K as a promising target for melanoma therapy.