bluuebunny/crossref_metadata_2025 huggingface dataset:
(3-Chloroacetyl)-indole, a Novel Allosteric AKT Inhibitor, Suppresses Colon Cancer Growth In Vitro and In Vivo
Authors: Kim Dong Joon , Reddy Kanamata , Kim Myoung Ok , Li Yan , Nadas Janos , Cho Yong-Yeon , Kim Jong-Eun , Shim Jung-Hyun , Song Nu Ry , Carper Andria , Lubet Ronald A. , Bode Ann M. , Dong Zigang
Published: September 2011

Indole-3-carbinol (I3C) is produced in Brassica vegetables such as broccoli and cabbage and has been shown to inhibit proliferation and induce apoptosis in various cancer cells, including breast, prostate, colon, and leukemia. However, only high doses of I3C were shown to inhibit cell proliferation (IC50 = 200–300 μmol/L). Our goal here was to develop a more potent antitumor agent by modifying the structure of I3C. We created I3C derivatives and found that (3-chloroacetyl)-indole (3CAI) more strongly inhibited colon cancer cell growth than I3C. In addition, by screening 85 kinases in a competitive kinase assay, we found that 3CAI was a specific AKT inhibitor. AKT is a serine/threonine kinase that plays a pivotal role in promoting transformation and chemoresistance by inducing proliferation and inhibiting apoptosis. Therefore, AKT is regarded as a critical target for cancer therapy. 3ICA, a derivative of I3C, is a potent and specific AKT inhibitor. This compound showed significant inhibition of AKT in an in vitro kinase assay and suppressed expression of AKT direct downstream targets such as mTOR and GSK3β as well as induced growth inhibition and apoptosis in colon cancer cells. In addition, oral administration of this potent AKT inhibitor suppressed cancer cell growth in an in vivo xenograft mouse model. Cancer Prev Res; 4(11); 1842–51. ©2011 AACR.
Deficient p27 Phosphorylation at Serine 10 Increases Macrophage Foam Cell Formation and Aggravates Atherosclerosis Through a Proliferation-Independent Mechanism
Authors: Fuster José J. , González-Navarro Herminia , Vinué Angela , Molina-Sànchez Pedro , Andrés-Manzano Maria J. , Nakayama Keiichi I. , Nakayama Keiko , Díez-Juan Antonio , Bernad Antonio , Rodríguez Cristina , Martínez-González José , Andrés Vicente
Published: September 2011

Objective—

Genetic ablation of the growth suppressor p27
Kip1
(p27) in the mouse aggravates atherosclerosis coinciding with enhanced arterial cell proliferation. However, it is unknown whether molecular mechanisms that limit p27's protective function contribute to atherosclerosis development and whether p27 exerts proliferation-independent activities in the arterial wall. This study aims to provide insight into both questions by investigating the role in atherosclerosis of p27 phosphorylation at serine 10 (p27-phospho-Ser10), a major posttranslational modification of this protein.

Methods and Results—

Immunoblotting studies revealed a marked reduction in p27-phospho-Ser10 in atherosclerotic arteries from apolipoprotein E–null mice, and expression of the nonphosphorylatable mutant p27Ser10Ala, either global or restricted to bone marrow, accelerated atherosclerosis. p27Ser10Ala expression did not affect cell proliferation in early and advanced atheroma but activated RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) signaling and promoted macrophage foam cell formation in a ROCK-dependent manner. Supporting the clinical relevance of these findings, human atherosclerotic coronary arteries exhibited a prominent reduction in p27-phospho-Ser10 and increased ezrin/radixin/moesin protein phosphorylation, a marker of RhoA/ROCK activation.

Conclusion—

Scarce phosphorylation of p27 at Ser10 is a hallmark of human and mouse atherosclerosis and promotes disease progression in mice. This proatherogenic effect is mediated by a proliferation-independent mechanism that involves augmented foam cell formation owing to increased RhoA/ROCK activity. These findings unveil a new atheroprotective action of p27 and identify p27-phospho-Ser10 as an attractive target for the treatment of atherosclerosis.
MicroRNA-16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1
Authors: Chamorro-Jorganes Aránzazu , Araldi Elisa , Penalva Luiz O.F. , Sandhu Devraj , Fernández-Hernando Carlos , Suárez Yajaira
Published: September 2011

Objective—

MicroRNAs play key roles in modulating a variety of cellular processes by posttranscriptional regulation of their target genes. Vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2), and fibroblast growth factor receptor-1 (FGFR1) were identified by bioinformatic approaches and subsequently validated as targets of microRNA (miR)-16 and miR-424 in endothelial cells (ECs).

Methods and Results—

Mimetics of these microRNAs reduced VEGF, VEGFR2, and FGFR1 expression, whereas specific antagonists enhanced their expression. Expression of mature miR-16 and miR-424 was upregulated on VEGF or basic fibroblast growth factor (bFGF) treatment. This upregulation was accompanied by a parallel increase in primary transcript (pri-miR)-16-1 and pri-miR-16-2 but not in pri-miR-424 levels, indicating a VEGF/bFGF-dependent transcriptional and posttranscriptional regulation of miR-16 and miR-424, respectively. Reduced expression of VEGFR2 and FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling through these receptors, thereby affecting the activity of downstream components of the pathways. Functionally, miR-16 or miR-424 overexpression reduced proliferation, migration, and cord formation of ECs in vitro, and lentiviral overexpression of miR-16 reduced the ability of ECs to form blood vessels in vivo.

Conclusion—

We conclude that these miRNAs fine-tune the expression of selected endothelial angiogenic mediators in response to these growth factors. Altogether, these findings suggest that miR-16 and miR-424 play important roles in regulating cell-intrinsic angiogenic activity of ECs.
Recent Patterns of Sex-Specific Midlife Stroke Hospitalization Rates in the United States
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: September 2011

Background and Purpose—

Little is known about sex-specific stroke hospitalization rates among middle-aged individuals. This study assessed recent temporal trends in stroke hospitalizations among persons aged 35 to 64 years in the United States.

Methods—

The Nationwide Inpatient Sample was used to identify individuals with a primary or secondary discharge diagnosis of stroke between 1997 and 2006 (n=3 161 752). Age-adjusted sex-specific rates of ischemic and hemorrhagic stroke hospitalizations were assessed among individuals aged 35 to 64 years.

Results—

Over the study period, stroke hospitalization rates per 100 000 decreased by 10% from 66.7 to 60.3 (trend
P
<0.01) in men and 8% from 52.7 to 48.3 (trend
P
<0.001) in women. The 55- to 64-year age group drove reductions in hospitalization rates: slope (rate of change per year)=−12.3 for men and −8.9 for women (both
P
<0.001). Rates increased slightly in men and women aged 35 to 44 years and remained stable for persons aged 45 to 54 years. Stroke subtype analysis revealed that rates of ischemic stroke hospitalization increased and hemorrhagic stroke hospitalization remained stable among individuals aged 35 to 44 years. Rates of ischemic and hemorrhagic stroke hospitalizations remained stable among those aged 45 to 54 years and decreased among persons aged 55 to 64 years.

Conclusions—

From 1997 to 2006, ischemic and hemorrhagic stroke hospitalization rates declined among individuals aged 55 to 64 years and remained stable among persons aged 45 to 54 years; ischemic stroke hospitalization rates increased among individuals aged 35 to 44 years. Further studies are needed to assess and address increases in ischemic stroke hospitalizations among younger individuals.
Telestroke-Guided Intravenous Tissue-Type Plasminogen Activator Treatment Achieves a Similar Clinical Outcome as Thrombolysis at a Comprehensive Stroke Center
Authors: Zaidi Syed F. , Jumma Mouhammad A. , Urra Xabier N. , Hammer Maxim , Massaro Lori , Reddy Vivek , Jovin Tudor , Lin Ridwan , Wechsler Lawrence R.
Published: September 2011

Background and Purpose—

Telestroke networks offer an opportunity to increase tissue-type plasminogen activator use in community hospitals.

Methods—

We compared 83 patients treated with intravenous tissue-type plasminogen activator by telestroke to 59 patients treated after in-person evaluation by the same neurologists at a tertiary care stroke center. Onset and door-to-treatment times and functional outcome at 90 days were obtained prospectively. Favorable outcome was defined as modified Rankin Scale score ≤2.

Results—

Favorable outcome rates were comparable between the groups (42.1% versus 37.5%,
P
=0.7). There was no significant difference in the rate of symptomatic hemorrhage.

Conclusions—

Telestroke is a viable alternative to in-person evaluation when stroke expertise is not readily available.
Testing the Construct Validity of the Gambling Functional Assessment–Revised
Authors: Weatherly Jeffrey N. , Miller Joseph C. , Terrell Heather K.
Published: September 2011

An attempt was made to modify the Gambling Functional Assessment (GFA), which was proposed to identify four possible contingencies maintaining the respondent’s gambling behavior. However, previous research found that it only identified two contingencies (i.e., positive vs. negative reinforcement), with some items cross-loading on both contingencies and one not loading at all. A total of 1,060 undergraduate students completed a revised version of the GFA containing 22 items. Exploratory factor analyses conducted on a random selection of half of the participants led to a two-factor solution (positive and negative reinforcement) for 16 of the items that strongly loaded on the two factors. Confirmatory factor analyses conducted using structural equation modeling on the data from the other half of the sample confirmed the two-factor model. The GFA–Revised consists of 16 items, 8 each measuring positive and negative reinforcement contingencies. Although this revised measure cleanly parses the two contingencies, the data indicate that gambling maintained by positive reinforcement is more frequent than gambling maintained by negative reinforcement. This outcome will make directly comparing the two contingencies difficult, especially given that evidence suggests that gambling maintained by negative reinforcement is more strongly associated with pathology than gambling maintained by positive reinforcement.
He Just Wants to Play
Authors: Denzler Markus , Häfner Michael , Förster Jens
Published: September 2011

Generally, the accessibility of goal-related constructs is inhibited upon goal fulfillment. In line with this notion, the current studies explored whether violent computer games may reduce relative accessibility of aggression if the game involves the fulfillment of an aggressive goal. Specifically, in Study 1, participants who watched a trailer for a violent computer game that fulfilled the goal of venting anger showed less relative accessibility of aggression compared to participants who watched the trailer without goal fulfillment. In Study 2, actually playing a violent computer game to vent anger also decreased the relative accessibility of aggression compared to a control condition in which the game was played without such a goal. Lastly, in Study 3, the relative accessibility of aggression was reduced after playing a violent computer game for participants who reported a high general tendency to vent their anger.
Does an Unplanned Pregnancy Have Long-Term Implications for Mother–Child Relationships?
Authors: Nelson Jackie A. , O’Brien Marion
Published: September 2011

The effect of pregnancy planning on the quality of mother–adolescent relationships 15 years later was examined among 373 first-time parents and 472 experienced parents using a mediated moderation model. Among first-time mothers only, the experience of an unplanned pregnancy was related to higher maternal depressive symptoms when mothers also experienced high parenting stress over the first three years. High maternal depressive symptoms over those early years were, in turn, related to more conflict and hostility in the parent–adolescent relationship according to mother and adolescent reports. Additionally, interactions between parity and pregnancy planning revealed that experienced mothers with unplanned pregnancies had the most early parenting stress, although an unplanned pregnancy and high parenting stress did not predict higher depressive symptoms for these mothers as it did for first-time mothers. The findings provide support for the importance of early parenting emotions and experiences on later parent–adolescent relationship quality.
Advanced Placement Course Enrollment and School-Level Characteristics
Authors: Barnard-Brak Lucy , McGaha-Garnett Valerie , Burley Hansel
Published: September 2011

The current study examined access to Advanced Placement (AP) courses as a function of these school characteristics (e.g., percentage of ethnic minority and lower socioeconomic status) and then examined AP course enrollment as a function of both access to AP courses and these school characteristics. Using structural equation modeling techniques, results indicated that school characteristics, such as the percentage of students who have minority and/or lower socioeconomic status backgrounds, would appear to be more related to the availability of AP curricula rather than to the number of students who enroll in these courses at a school.
‘Prayers of Petition’ in the Psalms and West Semitic Inscribed Amulets: Efficacious Words in Metal and Prayers for Protection in Biblical Literature
Authors: Smoak Jeremy D.
Published: September 2011

This article compares several Phoenician and Punic inscribed amulets to the language preserved in several psalms that petition YHWH for protection against evil or other types of danger. The fact that both the amulets and these particular psalms share a similar concern or function, namely, protection against evil, invites such a comparison. It is argued in this article that the similarities between the psalms and the amulets allow for the conclusion that both forms drew from a similar stock of words commonly employed in West Semitic apotropaic religious practices. In particular, it is argued that the protective formulae inscribed on the amulets, which bear certain similarities to the language employed in such psalms, indicate that the psalms contain more reflexes of apotropaic formulae than previously recognized.
Rethinking the Place and Purpose of Genesis 13
Authors: Rickett Dan
Published: September 2011

From reading the writings on Genesis 13 it is clear that, for many, the text has two main foci: (1) the separation of Abraham and Lot, the meaning of which has been variously interpreted by commentators, and/or (2) the promise of descendants. The promise of land, in contrast, is viewed, at best, as a secondary purpose within the narrative. Further, the character of Lot is seen solely in terms of his relationship to the blessing or his potential to be Abraham’s heir. However, these readings fail to see the separation of Abraham and Lot in light of the entirety of ch. 13 and the literary and theological connections between Genesis 13 and the command of Gen. 12.1 and the promise of 12.7. These connections point to two altogether different foci for ch. 13: (1) Abraham’s settlement in the land and (2) Abraham finally coming to the place of alignment with God’s command to separate himself fully from his father’s household. These foci lead to a new understanding of both Genesis 13 in general and the separation of Abraham and Lot in particular.
Design Empowerment
Authors: Senbel Maged , Church Sarah P.
Published: September 2011

Empowering community residents to participate in neighborhood design may help overcome the tension between the urban densification requirements of climate change planning and the political infeasibility of rapid change. This research employed accessible visualization media in public workshops to test the capacity of the media to enable empowerment. In a community facing imminent development we found processes of mitigated empowerment through which residents accessed and generated information, were inspired to act in the face of complex problems, and expressed their ideas. The media did not enable design empowerment in the areas of community inclusion or integration into the design process.
Staying power: the Eye has it
Authors: McEntee John
Published: September 2011

With the satirical magazine about to celebrate its 50th anniversary, gossip writer John McEntee assesses the reasons for its staying power. And he reveals, er, not much really, except that it’s likely to run and run and run (unlike Fergus Cashin).
Crusaders or pigs in raincoats?
Authors: Barnett Steven
Published: September 2011

The caped crusader versus the pigs The phone hacking scandal reveals the difference between two models of journalism and two models of journalist, argues Steven Barnett, professor of communications at the University of Westminster. Now is the time to stand up for the caped crusaders and to kill of the ‘pigs in raincoats.
Privacy? It’s secrecy by stealth
Authors: O'Brien James
Published: September 2011

The distinction between what is in the public interest as opposed to what interests the public is entirely nebulous, writes LBC phone-in host James O’Brien. He also believes that secrecy has been redefined as privacy and contends that journalists should have the right to report anything – as long as it is true.
When Prisoners Take Over the Prison
Authors: Haslam S. Alexander , Reicher Stephen D.
Published: September 2011

There is a general tendency for social psychologists to focus on processes of oppression rather than resistance. This is exemplified and entrenched by the Stanford Prison Experiment (SPE). Consequently, researchers and commentators have come to see domination, tyranny, and abuse as natural or inevitable in the world at large. Challenging this view, research suggests that where members of low-status groups are bound together by a sense of shared social identity, this can be the basis for effective leadership and organization that allows them to counteract stress, secure support, challenge authority, and promote social change in even the most extreme of situations. This view is supported by a review of experimental research—notably the SPE and the BBC Prison Study—and case studies of rebellion against carceral regimes in Northern Ireland, South Africa, and Nazi Germany. This evidence is used to develop a social identity model of resistance dynamics.
Immediacy and openness in a digital Africa: Networked-convergent journalisms in Kenya
Authors: Mudhai Okoth Fred
Published: September 2011

Before the US crackdown on the WikiLeaks website in 2010, the narrative of freedom dominating discourses on uneasy deployment of new information and communication technologies (ICTs) in journalism was more prevalent in Africa – and developing regions – than in advanced democracies. Little wonder WikiLeaks did not, at least initially, include African media partners in their potent 2010 ‘cablegate’ exposés. From the 1996 Zambian government ban of the Post online to the recent onslaughts on bloggers in parts of the continent, ICT uses in journalism have reflected national contexts, with restrictions often resulting in self-censorship, as well as innovations that borrow from and build on global developments. This ‘glocal’ context perspective defines the review here of the new media use in journalism in Africa with an examination of Kenyan media coverage – mainly between the 2005 and 2010 constitutional referenda. The focus is on coverage by two leading newspapers as they strive to keep up with emerging alternative spaces of networked online expression. The aim here is to determine the extent to which the coverage reflects immediacy and openness in a networked and converged environment, with implications for democracy. The article employs a comparative approach and qualitative content-genre analysis.
EZSCAN™ a new technology to detect diabetes risk
Authors: EH Schwarz Peter , Brunswick Philippe , Calvet Jean-Henri
Published: September 2011

Key to putting prevention of diabetes into practice is finding the people with increased risk. Several tools are currently in use: oral glucose tolerance test, fasting glucose measurement and a number of questionnaires to identify those with increased risk. Each has its own advantages and disadvantages. One new tool that can identify those with increased diabetes risk is the EZSCAN™. This new diagnostic device developed by Impeto Medical uses the sweat gland function to detect risk for insulin resistance and diabetes. The basic pathophysiology behind this technology is supported by the growing number of clinical studies worldwide which show a strong association between small nerve neuropathies to insulin resistance and diabetes risk. Because the EZSCAN™ test takes only three minutes to run, is non-invasive and easy to operate, it is an ideal diagnostic tool for both the medical and paramedical setting. Several applications are possible: the EZSCAN™ can be used to monitor insulin resistance-based treatment, to diagnose increased diabetes risk and to aid proposing diabetes prevention programmes. EZSCAN™ has the potential to become a very useful tool in diabetes risk diagnostics.
Life! in Australia: translating prevention research into a large-scale intervention
Authors: Reddy Prasuna , Rankins Debbie , Timoshanko Amy , Dunbar James A
Published: September 2011

The increasing prevalence of type 2 diabetes is of great public health concern. In the state of Victoria, Australia, a group-based lifestyle intervention programme, Life! – Taking Action on Diabetes, was developed for people over the age of 50 years who are at high risk of diabetes. It aims to reduce the risk of diabetes by providing practical skills, including goal setting and problem solving, to encourage participants to adopt a healthy diet and active lifestyle. The programme is delivered by specially trained facilitators who have undergone an accredited three-stage training programme. A quality assurance process is also in place to ensure that it is delivered to a consistently high standard. The Life! program is a direct progression from the Finnish randomised controlled trial and the Greater Green Triangle Diabetes Prevention Project implementation trial. This paper describes how a diabetes prevention programme was implemented at a state-wide level and the training of facilitators to conduct the group sessions. Future studies are needed to examine the cost effectiveness and development of specific programmes for diverse population groups.
An Approach to Assessing Data Quality in an Area Probability Survey Using CBPR
Authors: Rucinski Dianne , Davis Rochelle , Gomez Guillermo , Flores Jovita , Perez Idida , Zanoni Joseph
Published: September 2011

Community-based participatory research (CBPR) approaches attempt to engage community members in all aspects of research conducted in the community. Proponents of CBPR suggest that among the many advantages to using CBPR is higher acceptance of and cooperation in research endeavors than is usually achieved through more traditional research approaches. Using secondary analysis of sample disposition data from two area probability surveys of the same community areas, one involving community interviewers in a fully collegial CBPR study and the other using professional interviewers, this study finds that data collected using CBPR techniques may lead to higher cooperation and lower refusal rates than data collected by professional interviewers. However, when compared to external population indicators such as census data, the sample produced by CBPR interviewers overrepresents certain population groups whereas the survey data produced by professional interviewers may underrepresent key population groups.
Medication Error Prevention in the School Setting
Authors: Richmond Sandra L.
Published: September 2011

Empirical evidence has identified that medication errors occur in the school setting; however, there is little research that identifies medication error prevention strategies specific to the school environment. This article reviews common medication errors that occur in the school setting and presents potential medication prevention strategies, such as developing medication error reporting systems, using technology, reviewing systems and processes that support current medication administration practices, and limiting distractions. The Standards of Professional Performance developed by the National Association of School Nurses identifies the need for school nurses to enhance the quality and effectiveness of their practice. Improving the safety of medication administration and preventing medication errors are examples of how nurses can demonstrate meeting this standard.
High School Students’ Participation in Music Activities Beyond the School Day
Authors: Kuntz Tammy L.
Published: September 2011

The purpose of this qualitative study was to investigate the music activities that high school band students are involved in and how these activities might lead to lifelong music participation. Specific research questions were the following: (a) In what activities are high school band students involved? (b) What are high school band directors doing to encourage lifelong participation in music? (c) How do students describe their plans for musical involvement in the future? Three focus group discussions at one rural school ( n = 5), one suburban school ( n = 5), and one urban school ( n = 4) were conducted to discover ways students participated in music activities beyond the school day. These opportunities ranged from cultural groups, to community youth events, to time with friends listening to music. Influences of family members and the desire to maintain connections seem to be beneficial in creating musicians with a desire for music participation as adults.
Musical Development and Learning Characteristics of Students
Authors: Gooding Lori , Standley Jayne M.
Published: September 2011

Development involves progressive changes in knowledge and abilities that occur across the life span. Current research on musical abilities suggests that the development of skills necessary for musicality begins in utero and continues through adulthood. Many of these skills, such as the ability to carry a tune, move in time to music, and respond emotionally to music, progress as part of normal cognitive maturation and development. Others, such as explicit musical knowledge and musical performance, require in-depth learning and practice for future musical development to occur. This article provides a compilation of key musical developmental milestones and learning characteristics from prebirth through adolescence gathered from the research literature. A brief summary of relevant information is provided, as well as charts outlining specific points from the literature.
A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation
Authors: Neven Bénédicte , Magerus-Chatinet Aude , Florkin Benoit , Gobert Delphine , Lambotte Olivier , De Somer Lien , Lanzarotti Nina , Stolzenberg Marie-Claude , Bader-Meunier Brigitte , Aladjidi Nathalie , Chantrain Christophe , Bertrand Yves , Jeziorski Eric , Leverger Guy , Michel Gérard , Suarez Felipe , Oksenhendler Eric , Hermine Olivier , Blanche Stéphane , Picard Capucine , Fischer Alain , Rieux-Laucat Frédéric
Published: September 2011

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder characterized by early-onset, chronic, nonmalignant lymphoproliferation, autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS) of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have been described previously, long-term follow-up data on morbidity and mortality are scarce. We performed a retrospective analysis of clinical and genetic features of 90 ALPS-FAS and ALPS-sFAS patients monitored over a median period of 20.5 years. Heterozygous germline mutations of TNFRSF6 were identified in 83% of probands. Somatic TNFRSF6 mutations were found in 17% of index cases (all located within the intracellular domain of FAS). Sixty percent of the ALPS-FAS patients with mutations in the extracellular domain had a somatic mutation affecting the second allele of TNFRSF6; age at onset was later in these patients. No other genotype-phenotype correlations could be found. Long-term analysis confirmed a trend toward spontaneous remission of lymphoproliferation in adulthood but mixed outcomes for autoimmune manifestations. We observed significant and potentially life-threatening disease and treatment-related morbidity, including a high risk of sepsis after splenectomy that calls for careful long-term monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients.
Physiological changes during low- and high-intensity noninvasive ventilation
Authors: Lukácsovits J. , Carlucci A. , Hill N. , Ceriana P. , Pisani L. , Schreiber A. , Pierucci P. , Losonczy G. , Nava S.
Published: September 2011

In a physiological randomised cross-over study performed in stable hypercapnic chronic obstructive disease patients, we assessed the short-term effects of two settings of noninvasive ventilation.

One setting was aimed at maximally reducing arterial carbon dioxide tension (Pa,CO2) (high-intensity (Hi) noninvasive positive pressure ventilation (NPPV)): mean±sd27.6±2.1 cmH2O of inspiratory positive airway pressure, 4±0 cmH2O of expiratory positive airway pressure and respiratory rate of 22 breaths·min−1. The other was performed according to the usual parameters used in earlier studies (low-intensity (Li)-NPPV): 17.7±1.6 cmH2O of inspiratory positive airway pressure, 4±0 cmH2O of expiratory positive airway pressure and respiratory rate of 12 breaths·min−1.

Both modes of ventilation significantly improved gas exchange compared with spontaneous breathing (SB), but to a greater extent using Hi-NPPV (Pa,CO259.3±7.5, 55.2±6.9 and 49.4±7.8 mmHg for SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater reduction in the pressure–time product of the diaphragm per minute from 323±149 cmH2O·s·min−1during SB to 132±139 cmH2O·s·min−1during Li-NPPV and 40±69 cmH2O·s·min−1during Hi-NPPV, while in nine out of 15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked reduction in cardiac output (CO) measured noninvasively with a Finometer PRO (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV.

We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in CO, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.
Clinical presentation and outcome of venous thromboembolism in COPD
Authors: Bertoletti L. , Quenet S. , Mismetti P. , Hernández L. , Martín-Villasclaras J.J. , Tolosa C. , Valdés M. , Barrón M. , Todolí J.A. , Monreal M. ,   the RIETE Investigators
Published: September 2011

Chronic obstructive pulmonary disease (COPD) is a moderate risk factor for venous thromboembolism (VTE), but neither the clinical presentation nor the outcome of VTE in COPD patients is well known.

The clinical presentation of VTE, namely pulmonary embolism (PE) or deep venous thrombosis (DVT), and the outcome at 3 months (death, recurrent VTE or bleeding) were compared between 2,984 COPD patients and 25,936 non-COPD patients included in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. This ongoing international, multi-centre registry includes patients with proven symptomatic PE or DVT.

PE was the more frequent VTE presentation in COPD patients (n=1,761, 59%). PE presentation was more significantly associated with COPD patients than non-COPD patients (OR 1.64, 95% CI 1.49–1.80). During the 3-month follow-up, mortality (10.8%versus7.6%), minor bleeding (4.5%versus2.3%) or first VTE recurrences as PE (1.5%versus1.1%) were significantly higher in COPD patients than in non-COPD patients. PE was the most common cause of death.

COPD patients presented more frequently with PE than DVT. It may explain the worse prognosis of COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE compared with non-COPD patients. Further therapeutic options are needed.
Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial hypertension
Authors: Heresi G.A. , Tang W.H.W. , Aytekin M. , Hammel J. , Hazen S.L. , Dweik R.A.
Published: September 2011

Circulating cardiac troponins are markers of myocardial injury. We sought to determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is associated with disease severity and prognosis in pulmonary arterial hypertension (PAH).

cTnI was measured in 68 patients with PAH diagnostic category 1 in a research-based sensitive immunoanalyser with a lower limit of detection of 0.008 ng·mL−1. The associations between cTnI and PAH severity and clinical outcomes were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan–Meier analysis and Cox regression models.

cTnI was detected in 25% of patients. Patients with detectable cTnI had more advanced functional class symptoms, a shorter 6-min walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels. 36-month transplant-free survival was 44% in patients with detectable cTnIversus85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold increased risk of death related to right ventricular failure or transplant (hazard ratio 4.74, 95% CI 1.89–11.89; p<0.001), even when adjusted individually for known parameters of PAH severity.

Elevated plasma cTnI, even at subclinically detectable levels, is associated with more severe disease and worse outcomes in patients with PAH.
With good intentions: complexity in unsolicited informal support for Aboriginal and Torres Strait Islander peoples. A qualitative study
Authors: Ward Nathaniel J , Jowsey Tanisha , Haora Penny J , Aspin Clive , Yen Laurann E
Published: September 2011

Background

Understanding people's social lived experiences of chronic illness is fundamental to improving health service delivery and health outcomes, particularly in relation to self-management activity. In explorations of social lived experiences this paper uncovers the ways in which Aboriginal and Torres Strait Islander people with chronic illness experience informal unsolicited support from peers and family members.

Methods

Nineteen Aboriginal and Torres Islander participants were interviewed in the Serious and Continuing Illness Policy and Practice Study (SCIPPS). Participants were people with Type 2 diabetes (N = 17), chronic obstructive pulmonary disease (N = 3) and/or chronic heart failure (N = 11) and family carers (N = 3). Participants were asked to describe their experience of having or caring for someone with chronic illness. Content and thematic analysis of in-depth semi-structured interviews was undertaken, assisted by QSR Nvivo8 software.

Results

Participants reported receiving several forms of unsolicited support, including encouragement, practical suggestions for managing, nagging, growling, and surveillance. Additionally, participants had engaged in 'yarning', creating a 'yarn' space, the function of which was distinguished as another important form of unsolicited support. The implications of recognising these various support forms are discussed in relation to responses to unsolicited support as well as the needs of family carers in providing effective informal support.

Conclusions

Certain locations of responsibility are anxiety producing. Family carers must be supported in appropriate education so that they can provide both solicited and unsolicited support in effective ways. Such educational support would have the added benefit of helping to reduce carer anxieties about caring roles and responsibilities. Mainstream health services would benefit from fostering environments that encourage informal interactions that facilitate learning and support in a relaxed atmosphere.
Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas
Authors: Lind Guro E , Danielsen Stine A , Ahlquist Terje , Merok Marianne A , Andresen Kim , Skotheim Rolf I , Hektoen Merete , Rognum Torleiv O , Meling Gunn I , Hoff Geir , Bretthauer Michael , Thiis-Evensen Espen , Nesbakken Arild , Lothe Ragnhild A
Published: September 2011

Background

The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas.

Methods

Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel.

Results

Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa.

Conclusions

The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.
Organic-skinned inorganic nanoparticles: surface-confined polymerization of 6-(3-thienyl)hexanoic acid bound to nanocrystalline TiO2
Authors: Saji Viswanathan S , Jo Yimhyun , Moon Hoi Ri , Jun Yongseok , Song Hyun-Kon
Published: September 2011

There are many practical difficulties in direct adsorption of polymers onto nanocrystalline inorganic oxide surface such as Al2O3 and TiO2 mainly due to the insolubility of polymers in solvents or polymer agglomeration during adsorption process. As an alternative approach to the direct polymer adsorption, we propose surface-bound polymerization of pre-adsorbed monomers. 6-(3-Thienyl)hexanoic acid (THA) was used as a monomer for poly[3-(5-carboxypentyl)thiophene-2,5-diyl] (PTHA). PTHA-coated nanocrystalline TiO2/FTO glass electrodes were prepared by immersing THA-adsorbed electrodes in FeCl3 oxidant solution. Characterization by ultraviolet/visible/infrared spectroscopy and thermal analysis showed that the monolayer of regiorandom-structured PTHA was successfully formed from intermolecular bonding between neighbored THA surface-bound to TiO2. The anchoring functional groups (-COOH) of the surface-crawling PTHA were completely utilized for strong bonding to the surface of TiO2.
Cardiac tamponade and paroxysmal third-degree atrioventricular block revealing a primary cardiac non-Hodgkin large B-cell lymphoma of the right ventricle: a case report
Authors: Frikha Zied , Abid Leila , Abid Dorra , Mallek Souad , Frikha Imed , Abdennadher Mohamed , Rekik Noomen , Kammoun Samir
Published: September 2011

Introduction

Primary cardiac lymphoma is rare.

Case Presentation

We report the case of a 64-year-old non-immunodeficient Caucasian man, with cardiac tamponade and paroxysmal third-degree atrioventricular block. Echocardiography revealed the presence of a large pericardial effusion with signs of tamponade and a right ventricular mass was suspected. Scanner investigations clarified the sites, extension and anatomic details of myocardial and pericardial infiltration. Surgical resection was performed due to the rapid impairment of his cardiac function. Analysis of the pericardial fluid and histology confirmed the diagnosis of non-Hodgkin large B-cell lymphoma. He was treated with chemotherapy.

Conclusion

The prognosis remains poor for this type of tumor due to delays in diagnosis and the importance of the site of disease.
Rapid analysis of formic acid, acetic acid, and furfural in pretreated wheat straw hydrolysates and ethanol in a bioethanol fermentation using atmospheric pressure chemical ionisation mass spectrometry
Authors: Davies Scott M , Linforth Rob S , Wilkinson Stuart J , Smart Katherine A , Cook David J
Published: September 2011

Atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) offers advantages as a rapid analytical technique for the quantification of three biomass degradation products (acetic acid, formic acid and furfural) within pretreated wheat straw hydrolysates and the analysis of ethanol during fermentation. The data we obtained using APCI-MS correlated significantly with high-performance liquid chromatography analysis whilst offering the analyst minimal sample preparation and faster sample throughput.
The β-Catenin Binding Protein ICAT Modulates Androgen Receptor Activity
Authors: Zhuo Ming , Zhu Chunfang , Sun JingLucy , Weis William I. , Sun Zijie
Published: September 2011

Androgens have important roles in the development of the prostate gland and in prostate cancer. Since the finding that β-catenin is a cofactor of the androgen receptor (AR) and can augment AR signaling, several proteins have been found to affect AR signaling through their interaction with β-catenin. Here, we investigated inhibitor of β-catenin and T-cell factor (ICAT), a β-catenin binding protein that inhibits the canonical Wnt/β-catenin signaling pathway, in AR signaling. We demonstrated that expression of ICAT in two AR positive prostate cancer cell lines, LNCaP and LAPC4, augments ligand-dependent AR-mediated transcription. In contrast, short hairpin RNA knockdown of ICAT and β-catenin specifically blocks enhanced AR-mediated transcription by ICAT. Using both stable expression of ICAT and short hairpin RNA knockdown of ICAT expression approaches, we further showed that ICAT enhances expression of endogenous PSA and KLK2, two androgen response genes, and ligand-induced cell growth. In addition, we identified that ICAT and AR can form a ternary complex with β-catenin using in vitro glutathione S-transferase protein pulldown assays. Moreover, we detected the endogenous protein complex containing ICAT, AR, and β-catenin in prostate cancer cells using immunoprecipitation assays. Recruitment of endogenous ICAT onto the promoter region of the human PSA gene, an AR downstream target promoter, was also identified in LNCaP cells. Finally, using in vitro protein binding assays, we examined the effect of full-length and truncated ICAT on the AR-β-catenin interaction and observed that addition of full-length ICAT retained the interaction between β-catenin and AR proteins. Intriguingly, the truncated ICAT comprising the N-terminal helical domain showed a more pronounced effect on β-catenin binding to AR proteins. Our findings suggest a novel molecular mechanism underlying the cross talk between androgen and Wnt signaling pathways.
A national audit of estimated glomerular filtration rate and proteinuria reporting in the UK
Authors: Kilpatrick Eric S , Verrill Helen
Published: September 2011

Background

Within the UK there has been a rapid move to include the reporting of estimated glomerular filtration rate (eGFR) values to identify patients with chronic kidney disease (CKD). Guidance has also changed since its original introduction. This national audit aimed to establish how eGFR is reported by laboratories within the UK.

Methods

A questionnaire was sent to 164 UK National Health Service laboratories, which included questions on the patient groups who had eGFR reported, the eGFR thresholds used, adjustments made for ethnicity and the means of identifying proteinuria. The audit standards used were based on the 2008 National Institute for Health and Clinical Excellencec (NICE) CKD guidance.

Results

One hundred and thirty-one of the 164 laboratories (80%) responded. Forty-six percent reported eGFR on all adult requests while 36% limited use to general practitioners. Twenty-one percent did not issue eGFR to any inpatient. Sixty-two percent and 30% of laboratories had an upper reporting limit of ≥90 and ≥60 mL/min/1.73 m2, respectively; the remainder having higher thresholds. Sixty percent cited an ethnicity ‘correction factor’ on the report, 59% in a guideline but 28% in neither. An albumin:creatinine ratio was used by 63% to detect non-diabetic proteinuria, while 37% exclusively used a protein:creatinine ratio.

Conclusions

There has been rapid implementation of eGFR reporting in the UK since 2006. However, there is considerable variation in the way it is reported, with few laboratories currently exactly matching existing NICE recommendations. A reassessment of biochemical CKD assessment by most laboratories following a reiteration and clarification of current recommendations seems warranted.
The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease
Authors: He Jinhan , Lee Jung Hoon , Febbraio Maria , Xie Wen
Published: September 2011

The fatty acid translocase (FAT)/CD36 belongs to the class B scavenger receptor family. In addition to the known functions of CD36 in the uptake of oxidized low-density lipoprotein by macrophages and uptake of fatty acids by adipose tissues, skeletal muscle and heart, emerging evidence has pointed to an equally important function of CD36 in the uptake of fatty acids in the liver and the pathogenesis of fatty liver disease. Recent reports have also suggested CD36 as a shared transcriptional target of several ligand-sensing and lipogenic transcriptional factors, such as the aryl hydrocarbon receptor, and several nuclear hormone receptors, such as pregnane X receptor, liver X receptor and peroxisome proliferator activated receptor γ. Non-alcoholic fatty liver disease is common and medically significant, because it is closely related to metabolic syndrome and has a potential to progress into the more harmful non-alcoholic steatohepatitis. It is hoped that CD36 and their transcriptional regulators can represent novel therapeutic targets for the prevention and management of fatty liver disease.
The gumma and the gonad: syphilitic orchitis, a rare presentation of testicular swelling
Authors: Mackenzie H , Mahmalji W , Raza A
Published: September 2011

A 47-year-old man presented to his general practitioner (GP) with painful swelling of his right testis. He was diagnosed with epididymo-orchitis and a two-week course of erythromycin 500 mg four times daily was prescribed by his GP. Despite initial improvement, his symptoms persisted and he was referred to the local urology department. His sexual history revealed one lifetime sexual contact. A midstream urine sample grew non-lactose fermenting coliforms sensitive to ciprofloxacin and a two-week course of ciprofloxacin 500 mg two times daily was prescribed. Despite clinical improvement, a persistent suspicious abnormality on the ultrasound scan of his right testis prompted a right radical inguinal orchidectomy to exclude malignancy. Further diagnostic tests including histopathology excluded malignancy but confirmed tertiary syphilis. A comprehensive literature search revealed only 11 confirmed cases in the past 59 years.