bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart Disease May Be a Risk Factor for Pulmonary Embolism Without Peripheral Deep Venous Thrombosis
Authors: Sørensen Henrik T. , Horvath-Puho Erzsebet , Lash Timothy L. , Christiansen Christian F. , Pesavento Raffaele , Pedersen Lars , Baron John A. , Prandoni Paolo
Published: September 2011

Background—

Heart diseases increase the risk of arterial embolism; whether they increase the risk of pulmonary embolism without peripheral venous thrombosis is less certain.

Methods and Results—

We conducted a nationwide, population-based case-control study in Denmark using patients diagnosed with pulmonary embolism and/or deep venous thrombosis between 1980 and 2007. We computed odds ratios to estimate relative risks associating preceding heart disease with pulmonary embolism, pulmonary embolism and deep venous thrombosis, or deep venous thrombosis alone. In this study, 45 282 patients had pulmonary embolism alone, 4680 had pulmonary embolism and deep venous thrombosis, and 59 790 had deep venous thrombosis alone; 541 561 were population controls. Myocardial infarction and heart failure in the preceding 3 months conferred high risks of apparently isolated pulmonary embolism (odds ratio, 43.5 [95% confidence interval (CI), 39.6–47.8] and 32.4 [95% CI, 29.8–35.2], respectively), whereas the risks of combined pulmonary embolism and deep venous thrombosis (19.7 [95% CI, 16.0–24.2] and 22.1 [95% CI, 18.7–26.0], respectively) and deep venous thrombosis alone (9.6 [95% CI, 8.6–10.7] and 12.7 [95% CI, 11.6–13.9], respectively) were lower. Left-sided valvular disease was associated with an odds ratio of 13.5 (95% CI, 11.3–16.1), whereas the odds ratio was 74.6 (95% CI, 28.4–195.8) for right-sided valvular disease. Restricting the analysis to cases diagnosed after 2000 led to lower risk estimates but the same overall pattern.

Conclusion—

Heart diseases increase the near-term risk for pulmonary embolism not associated with diagnosed peripheral vein thrombosis.
Second Internal Thoracic Artery Versus Radial Artery in Coronary Artery Bypass Grafting
Authors: Ruttmann Elfriede , Fischler Nikolaus , Sakic Adel , Chevtchik Orest , Alber Hannes , Schistek Roland , Ulmer Hanno , Grimm Michael
Published: September 2011

Background—

The best second arterial conduit for multiple arterial revascularization (MAR) is still a matter of debate. Previous studies on the benefit of either using the radial artery (RA) or the right internal thoracic artery (RITA) in coronary artery bypass grafting are not conclusive. The aim of our study was to compare the perioperative and long-term outcome of either RA or RITA grafts as second conduits for MAR.

Methods and Results—

A consecutive series of 1001 patients undergoing first nonemergent coronary artery bypass grafting receiving either RA or RITA as second graft for MAR between 2001 and 2010 were studied. There were 277 patients receiving a RITA and 724 patients receiving a RA in addition to a left internal thoracic artery (LITA). Concomitant saphenous vein grafts (SVG) were grafted in addition as necessary. Propensity score–matched analysis was performed to compare the 2 groups, bilateral ITA±SVG (BITA±SVG group) and the LITA+RA±SVG group relative to overall survival and major adverse cardiac and cerebrovascular events–free survival. Hazard ratios and their 95% confidence intervals were estimated by COX regression stratified on matched pairs. The incidence of perioperative major adverse cardiac and cerebrovascular events was significantly lower in the BITA±SVG group (1.4% versus 7.6%,
P
<0.001). Overall survival (hazard ratio 0.23; 95% confidence interval 0.066–0.81;
P
=0.022) and major adverse cardiac and cerebrovascular events–free survival (hazard ratio 0.18; 95% confidence interval 0.08–0.42;
P
<0.001) were significantly better in the BITA±SVG group compared to the LITA+RA±SVG group.

Conclusions—

The results of our study provide strong evidence for the superiority of a RITA graft compared to RA as a second conduit in MAR.
Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom
Authors: Sachdev Vandana , Kato Gregory J. , Gibbs J. Simon R. , Barst Robyn J. , Machado Roberto F. , Nouraie Mehdi , Hassell Kathryn L. , Little Jane A. , Schraufnagel Dean E. , Krishnamurti Lakshmanan , Novelli Enrico M. , Girgis Reda E. , Morris Claudia R. , Rosenzweig Erika Berman , Badesch David B. , Lanzkron Sophie , Castro Oswaldo L. , Taylor James G. , Hannoush Hwaida , Goldsmith Jonathan C. , Gladwin Mark T. , Gordeuk Victor R.
Published: September 2011

Background—

Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults with sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively.

Methods and Results—

Echocardiography, 6-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the US and UK Walk–Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid regurgitation velocity, which reflects systolic pulmonary artery pressure, was 2.7 to <3.0 m/s (mean±SD, 2.8±0.1) in 26% of the subjects and ≥3.0 m/s (mean±SD, 3.4±0.4) in 11%. The LV lateral E/e′ ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in sickle cell disease, was significantly higher in the groups with tricuspid regurgitation velocity ≥2.7 m/s. Increased hemolysis (
P
<0.0001), LV lateral E/e′ ratio (
P
=0.0001), blood urea nitrogen (
P
=0.0002), and erythropoietin (
P
=0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex (
P
<0.0001), older age (
P
<0.0001), LV lateral E/e′ ratio (
P
=0.014), and tricuspid regurgitation velocity (
P
=0.019) were independent predictors of a shorter 6-minute walk distance.

Conclusions—

Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e′ ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LV diastolic dysfunction will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov.
Unique identifier: NCT00492531.
Placental Growth Factor Regulates Cardiac Inflammation Through the Tissue Inhibitor of Metalloproteinases-3/Tumor Necrosis Factor-α–Converting Enzyme Axis
Authors: Carnevale Daniela , Cifelli Giuseppe , Mascio Giada , Madonna Michele , Sbroggiò Mauro , Perrino Cinzia , Persico Maria Grazia , Frati Giacomo , Lembo Giuseppe
Published: September 2011

Background—

Heart failure is one of the leading causes of mortality and is primarily the final stage of several overload cardiomyopathies, preceded by an early adaptive hypertrophic response and characterized by coordinated cardiomyocyte growth, angiogenesis, and inflammation. Therefore, growth factors and cytokines have to be critically regulated during cardiac response to transverse aortic constriction. Interestingly, the dual properties of placental growth factor as an angiogenic factor and cytokine make it a candidate to participate in cardiac remodeling in response to hemodynamic overload.

Methods and Results—

After transverse aortic constriction, placental growth factor knockout mice displayed a dysregulation of cardiac remodeling, negatively affecting muscle growth. Molecular insights underscored that this effect was ascribable mainly to a failure in the establishment of adequate inflammatory response owing to an impaired activity of tumor necrosis factor-α–converting enzyme. Interestingly, after transverse aortic constriction, placental growth factor knockout mice had strongly increased levels of tissue inhibitor of metalloproteinases-3, the main natural TACE inhibitor, thus indicating an unbalance of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α–converting enzyme axis. Strikingly, when we used an in vivo RNA interference approach to reduce tissue inhibitor of metalloproteinases-3 levels in placental growth factor knockout mice during transverse aortic constriction, we obtained a complete phenotype rescue of early dilated cardiomyopathy.

Conclusions—

Our results demonstrate that placental growth factor finely tunes a balanced regulation of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α–converting enzyme axis and the consequent TNF-α activation in response to transverse aortic constriction, thus allowing the establishment of an inflammatory response necessary for adaptive cardiac remodeling.
Aortic Stiffness and Central Wave Reflections Predict Outcome in Renal Transplant Recipients
Authors: Verbeke Francis , Maréchal Céline , Van Laecke Steven , Van Biesen Wim , Devuyst Olivier , Van Bortel Luc M. , Jadoul Michel , Vanholder Raymond
Published: September 2011

Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659–0.776) for pulse wave velocity, 0.670 (95% CI 0.604–0.736) for central augmentation pressure, and 0.595 (95% CI 0.529–0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104–1.649;
P
=0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219–1.814;
P
<0.001) remained independent predictors of outcome. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in renal transplant recipients. As single parameter of wave reflection, central augmentation pressure was better than central augmentation index. Combined measurement of pulse wave velocity and central augmentation pressure may contribute to an accurate cardiovascular risk estimation in this heterogeneous population.
Can Response to Induction Chemotherapy Be a Predictive Marker for Ultimate Outcome in Hypopharyngeal Cancer?
Authors: Han Myung Woul , Ryu In Sun , Lee Sang‐Wook , Kim Sung‐Bae , Roh Jong‐Lyel , Choi Seung‐Ho , Kim Sang Yoon , Nam Soon Yuhl
Published: September 2011

Objective

Induction chemotherapy (ICT) may reduce rates of distant metastases and enhance organ preservation and survival rates in patients with hypopharyngeal cancer. The authors compared survival data in patients who underwent chemoradiotherapy or surgery after ICT and investigated whether response to ICT is a predictive marker for outcome in patients with hypopharyngeal cancer.

Study Design

Historical cohort study.

Setting

Tertiary‐care hospital.

Subjects and Methods

The authors enrolled 97 patients (89 men, 8 women; mean age 61.2 years; range, 29‐80 years) with previously untreated hypopharyngeal cancer who underwent ICT between January 1997 and December 2006 at Asan Medical Center. Disease‐free survival (DFS), overall survival (OS), and laryngectomy‐free survival (LFS) were analyzed.

Results

At a mean follow‐up of 38.0 months, the 3‐year DFS and OS for all patients were 48.3% and 49.2%, respectively. The 3‐year LFS rate of patients who underwent nonsurgical therapy (n = 85) after ICT was 48.0%. Only response to ICT was associated with DFS (P =. 047), OS (P =. 003), and LFS (P =. 009) in multivariate analysis. When the authors compared survival data in patients who underwent surgical and nonsurgical treatments after ICT, they found that there was no statistical difference in terms of the 3‐year DFS in partial response (42.9% vs 50.5%, P =. 77) and nonresponse groups (50.0% vs 0%, P =. 43) between the 2 treatment types.

Conclusion

ICT permits assessment of tumor responsiveness and alters subsequent therapy accordingly. Response to ICT may be useful in the prediction of ultimate outcomes and organ conservation in patients with hypopharyngeal cancer.
Examining the Influence of Development Patterns on Flood Damages along the Gulf of Mexico
Authors: Brody Samuel D. , Gunn Joshua , Peacock Walter , Highfield Wesley E.
Published: September 2011

The rising cost of floods is increasingly attributed to the pattern and form of the built environment. Our study empirically tests this notion by examining the relationship between development intensity and property damage caused by floods. We examine five years of insured flood loss claims across 144 counties and parishes fringing the Gulf of Mexico. Results indicate that clustered, high-intensity development patterns significantly reduce amounts of reported property damage, while increasing percentages of sprawling, low-intensity development involving recent conversion of open space greatly exacerbate flood losses. These findings demonstrate the importance of community development design in fostering flood-resilient communities.
Developing and Testing a Measure of Social Support With Mexican-Origin Pregnant Adolescents and Their Mother Figures
Authors: Umaña-Taylor Adriana J. , Updegraff Kimberly A. , White Rebecca M. B. , Herzog Melissa J. , Pflieger Jacqueline C. , Madden-Derdich Debra
Published: September 2011

The current study describes the development and psychometric testing of the Global Support From Mother Figure During Pregnancy Scale (GSMF-P). The measure is developed in both Spanish and English to assess social support provided to adolescents during their pregnancies. The current study examines the reliability, cross-language equivalence, and validity of the scale with a sample of 207 pregnant, Mexican-origin adolescents ( M age = 16.2, SD = 0.98) and their mother figures ( M age = 40.9, SD = 7.01). The scale demonstrates strong internal consistency across reporters and language versions. Furthermore, findings provide support for the measurement equivalence of the English and Spanish versions. Finally, all construct validity hypotheses are supported, providing initial evidence that the GSMF-P appears to be assessing the construct of mother figure social support from both adolescents’ and mother figures’ perspectives.
Delinking Destiny from Geography
Authors: Thakur Ramesh
Published: September 2011

The November 2008 terrorist attacks in Mumbai are analysed through six changing equations in India–Pakistan relations. The balance between military response and inaction is shifting towards the former. India has a vested but no longer critical interest in a strong and stable Pakistan. Pakistan’s deniability has been based on separation between the government, army, ISI and terrorists whose plausibility is fading. To reverse the worsening security situation, Pakistan’s military must be brought under full civilian control. Failing that, India will have to acquire the military capacity and political will to destroy the human and material infrastructure of terrorism in Pakistan. Finally, the rewards for Pakistan’s contributions to the war on terror in Afghanistan exceed penalties for its fuelling of terror in India. The structure of incentives and penalties must be reversed.
Revisiting Globalisation
Authors: Chowdhury Hasanuzzaman
Published: September 2011

’Capital’ has engulfed all other social constructs exalting the institutionalisation of property relations to its zenith to render capitalism its singular ubiquity. Conventional theories, including those of post-modernism or the notions of ‘social capital’ or ‘social business’, appear to be inadequate to grasp or assuage its antagonistic relations, rules and rationality. Capitalism acquired its current stature thriving first on autochthonous articulation of the economy and then harnessing ‘other economies’ to its own dynamics. This involved increased exploitation and appropriation of nature and labour necessitating increased subsumption of spatial loci and economies as ‘medium and soil’ and holding them in ‘uneven and combined development’ along with diverse modes of ‘militarism’. With global expansion and gargantuan accumulation, lately capitalism came to be designated as ‘globalisation’. Besides this benign appellation, earlier the ‘highest stage’ of capitalism was expounded as ‘imperialism’. Bangladesh, India or the South Asian subcontinent altogether, were a crucial part of this whole development though its current stance and impact is more diverse and even disconcerting for them owing to differential nature and/or degree of assimilation with globalisation. This article briefly examines globalisation in general and as it concerns Bangladesh in particular with some of its contemporary ramifications for the people and polity.
Let the Games Begin
Authors: Zimelis Andris
Published: September 2011

This article discusses the political role of the Olympic Games and its implications on the hosting country’s political and social life by analysing two cases—South Korea (1988) and Mexico (1968). Contrary to the belief that the games were created as an event that transcends politics, this study concludes that Olympic Games have been and are used as a political tool for various purposes and specific political circumstances eventually influenced the selection of Mexico’s and South Korea’s priorities for national development. Moreover, the findings of this article demonstrate that the Olympic Games served as a catalyst accelerating democratic changes in South Korea, and this finding can be applied to heuristic analysis of the future Olympic Games.
The Development of the Perceived School Experiences Scale
Authors: Anderson-Butcher Dawn , Amorose Anthony , Iachini Aidyn , Ball Annahita
Published: September 2011

Objectives: This article describes two studies related to the development of the Perceived School Experiences Scale (PSES). The PSES may be used by social workers to assess youths’ perceptions of three school-related protective factors, including school connectedness, academic press, and academic motivation. Method: In Study 1, exploratory and confirmatory analyses were conducted on a calibration ( n = 386) and cross-validation sample ( n = 387) of middle and high school students. In Study 2, test–retest reliability and predictive validity were established on a sample of high school students ( n = 97). Results: The resultant 14-item PSES demonstrated acceptable factorial validity and gender invariance in samples of middle and high school students. The PSES also demonstrated acceptable test–retest reliability, and correlated positively with perceived belonging and social competence. Conclusions: Overall, the PSES has important implications for social workers as they assess important protective factors and document the effectiveness of their interventions for the children and youth they serve.
No humans allowed? The alien in/as feminist theory
Authors: Kember Sarah
Published: September 2011

This article examines the role of the alien as the ultimate outsider and considers the challenges it poses to feminist theory. I argue that these challenges are based on the need to continue developing an ethics of relationality in which neither love nor relationality itself is deemed to be the answer; on rethinking agency and ontology in terms of becoming and the limitations of becoming; on a critique of representationalism which limits us to figuring the alien in rather than as feminist theory and thereby invokes the archetypal story in which alien and human, monster and human switch sides; and finally on reconsidering modes of communication that resonate with their theme and emphasise the performativity, conceptual risk taking and creativity that might enable feminist theory itself to become alien again.
Effects of Self-Affirmation on Implementation Intentions and the Moderating Role of Affect
Authors: Ferrer Rebecca A. , Shmueli Dikla , Bergman Hannah E. , Harris Peter R. , Klein William M. P.
Published: September 2011

Self-affirmation may offset defensiveness to threatening messages, increase intentions to engage in protective behaviors, and facilitate actual change. Relatively little is known about the conditions under which self-affirmation is most beneficial. The authors examined whether self-affirmation facilitates the forming of implementation intentions–plans to engage in specific steps that facilitate behavior change—and whether effects differ by affective state. Undergraduate female drinkers ( N = 265) were self-affirmed or not prior to reading an article linking excessive alcohol consumption to breast cancer susceptibility. They then had the opportunity to report implementation intentions, by listing specific steps they planned to take to reduce consumption. Consistent with predictions, self-affirmation promoted formation of implementation intentions, an effect found only among individuals manifesting positive (as opposed to negative) affect following receipt of the message. Self-affirmation may facilitate behavior change by encouraging development of implementation intentions, an effect that is likely enhanced among those experiencing positive affect.
Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol
Authors: Trottestam Helena , Horne AnnaCarin , Aricò Maurizio , Egeler R. Maarten , Filipovich Alexandra H. , Gadner Helmut , Imashuku Shinsaku , Ladisch Stephan , Webb David , Janka Gritta , Henter Jan-Inge ,   for the Histiocyte Society
Published: September 2011

Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P < .001), were more often female (P = .011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects.
Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation
Authors: Zamagni Elena , Patriarca Francesca , Nanni Cristina , Zannetti Beatrice , Englaro Emanuela , Pezzi Annalisa , Tacchetti Paola , Buttignol Silvia , Perrone Giulia , Brioli Annamaria , Pantani Lucia , Terragna Carolina , Carobolante Francesca , Baccarani Michele , Fanin Renato , Fanti Stefano , Cavo Michele
Published: September 2011

We prospectively analyzed the prognostic relevance of positron emission tomography–computed tomography (PET/CT) at diagnosis, after thalidomide-dexamethasone (TD) induction therapy and double autotransplantation (ASCT) in 192 newly diagnosed multiple myeloma (MM) patients. Presence at baseline of at least 3 focal lesions (FLs; 44% of cases), a standardized uptake value (SUV) > 4.2 (46%), and extramedullary disease (EMD; 6%) adversely affected 4-year estimates of progression-free survival (PFS; ≥ 3 FLs: 50%; SUV > 4.2: 43%; presence of EMD: 28%). SUV > 4.2 and EMD were also correlated with shorter overall survival (OS; 4-year rates: 77% and 66%, respectively). Persistence of SUV > 4.2 after TD induction was an early predictor for shorter PFS. Three months after ASCT, PET/CT was negative in 65% of patients whose 4-year rates of PFS and OS were superior to those of PET-positive patients (PFS: 66% and OS: 89%). In a multivariate analysis, both EMD and SUV > 4.2 at baseline and persistence of fluorodeoxyglucose (FDG) uptake after ASCT were independent variables adversely affecting PFS. PET/CT involvement at diagnosis, after novel agent-based induction and subsequent ASCT is a reliable predictor of prognosis in MM patients. This study is registered at www.clinicaltrials.gov as NTC01341262.
The putative Notch ligand HyJagged is a transmembrane protein present in all cell types of adult Hydra and upregulated at the boundary between bud and parent
Authors: Prexl Andrea , Münder Sandra , Loy Bernhard , Kremmer Elisabeth , Tischer Susanne , Böttger Angelika
Published: September 2011

Background

The Notch signalling pathway is conserved in pre-bilaterian animals. In the Cnidarian Hydra it is involved in interstitial stem cell differentiation and in boundary formation during budding. Experimental evidence suggests that in Hydra Notch is activated by presenilin through proteolytic cleavage at the S3 site as in all animals. However, the endogenous ligand for HvNotch has not been described yet.

Results

We have cloned a cDNA from Hydra, which encodes a bona-fide Notch ligand with a conserved domain structure similar to that of Jagged-like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult Hydra by in situ hybridisation but is strongly upregulated and easily visible at the border between bud and parent shortly before bud detachment. In contrast, HyJagged protein is found in all cell types of an adult hydra, where it localises to membranes and endosomes. Co-localisation experiments showed that it is present in the same cells as HvNotch, however not always in the same membrane structures.

Conclusions

The putative Notch ligand HyJagged is conserved in Cnidarians. Together with HvNotch it may be involved in the formation of the parent-bud boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and HyJagged indicate a more widespread function for these two transmembrane proteins in the adult hydra, which may be regulated by additional factors, possibly involving endocytic pathways.
How often is a work-up for Legionella pursued in patients with pneumonia? A retrospective study
Authors: Hollenbeck Brian , Dupont Irene , Mermel Leonard A
Published: September 2011

Background

It is unclear how often patients with pneumonia are assessed forLegionellain endemic areas. Additionally, the sensitivity of the IDSA/ATS criteria for recommendedLegionellatesting is undefined.

Methods

We performed a single-center, retrospective study of patients diagnosed withLegionellapneumonia at our hospital to determine: 1) how oftenLegionelladiagnostic testing is obtained on patients with pneumonia at the time of hospitalization or when pneumonia developed during hospitalization; and 2) how often patient's withLegionellapneumonia met at least one of the five criteria in the IDSA/ATS guidelines recommending a work-up forLegionella. Patients withLegionellapneumonia were identified using an infection control software program. Medical records of these patients were then reviewed.

Results

Thirty-five percent of patients with a discharge diagnosis of pneumonia hadLegionellaurine antigen testing and/or aLegionellaculture performed. Forty-four percent of patients who had a bronchoscopic specimen sent for microbiologic testing had aLegionellaculture performed on the bronchoscopic specimen and/orLegionellaurine antigen testing. Of 37 adult patients withLegionellapneumonia, 22 (59%) met the IDSA-ATS criteria recommendingLegionellatesting.

Conclusion

Following current recommendations forLegionellatesting missed 41% ofLegionellacases in adults in our single-center study. A work-up forLegionella(i.e., urine antigen test and/or culture) was performed in less than half of patients who have a bronchoscopic specimen sent for microbiologic testing.
Impact of information letters on the reporting rate of adverse drug reactions and the quality of the reports: a randomized controlled study
Authors: Johansson Marie-Louise , Hägg Staffan , Wallerstedt Susanna M
Published: September 2011

Background

Spontaneous reporting of adverse drug reactions (ADRs) is an important method for pharmacovigilance, but under-reporting and poor quality of reports are major limitations. The aim of this study was to evaluate if repeated one-page ADR information letters affect (i) the reporting rate of ADRs and (ii) the quality of the ADR reports.

Methods

All 151 primary healthcare units in the Region Västra Götaland, Sweden, were randomly allocated (1:1) to an intervention (n = 77) or a control group (n = 74). The intervention consisted of one-page ADR information letters administered at three occasions during 2008 to all physicians and nurses in the intervention units. The number of ADR reports received from the 151 units was registered, as was the quality of the reports, which was defined as high if the ADR was to be reported according to Swedish regulations, that is, if the ADR was (i) serious, (ii) unexpected, and/or (iii) related to the use of new drugs and not labelled as common in the Summary of Product Characteristics. A questionnaire was administered to evaluate if the ADR information letter had reached the intended recipient.

Results

Before the intervention, no significant differences in reporting rate or number of high quality reports could be detected between the randomization groups. In 2008, 79 reports were sent from 37 intervention units and 52 reports from 30 control units (mean number of reports per unit ± standard deviation: 1.0 ± 2.5 vs. 0.7 ± 1.2, P = 0.34). The number of high quality reports was higher in intervention units than in control units (37 vs. 15 reports, 0.5 ± 0.9 vs. 0.2 ± 0.6, P = 0.048). According to the returned questionnaires (n = 1,292, response rate 57%), more persons in the intervention than in the control group had received (29% vs. 19%, P < 0.0001) and read (31% vs. 26%, P < 0.0001) an ADR information letter.

Conclusions

This study suggests that repeated ADR information letters to physicians and nurses do not increase the ADR reporting rate, but may increase the number of high quality reports.
A multi-nutrient supplement reduced markers of inflammation and improved physical performance in active individuals of middle to older age: a randomized, double-blind, placebo-controlled study
Authors: Dunn-Lewis Courtenay , Kraemer William J , Kupchak Brian R , Kelly Neil A , Creighton Brent A , Luk Hui-Ying , Ballard Kevin D , Comstock Brett A , Szivak Tunde K , Hooper David R , Denegar Craig R , Volek Jeff S
Published: September 2011

Background

While exercise acts to combat inflammation and aging, the ability to exercise may itself be compromised by inflammation and inflammation's impact on muscle recovery and joint inflammation. A number of nutritional supplements have been shown to reduce inflammation and improve recovery. The purpose of the current investigation was to examine the effect of a multi-nutrient supplement containing branched chain amino acids, taurine, anti-inflammatory plant extracts, and B vitamins on inflammatory status, endothelial function, physical function, and mood in middle-aged individuals.

Methods

Thirty-one healthy and active men (N = 16, mean age 56 ± 6.0 yrs) and women (N = 15, mean age = 52 ± 7.5 yrs) participated in this investigation. Subjects completed one 28 day cycle of placebo supplementation and one 28 day cycle of multi-nutrient supplementation (separated by a one week washout period) in a balanced, randomized, double-blind, cross-over design. Subjects completed weekly perceptual logs (PROMIS-57, KOOS) and pre- and post- testing around the supplementation period. Testing consisted of brachial artery flow mediated dilation (FMD), blood measures, and physical performance on vertical jump, handgrip strength, and balance (dispersion from center of pressure). Significance for the investigation was p ≤ 0.05.

Results

IL-6 significantly decreased in both men (from 1.2 ± 0.2 to 0.7 ± 0.4 pg·mL-1) and women (from 1.16 ± 0.04 to 0.7 ± 0.4 pg·mL-1). Perceived energy also improved for both men (placebo: 1.8 ± 0.7; supplement: 3.7 ± 0.8 AUC) and women (placebo: 1.2 ± 0.7; supplement: 2.8 ± 0.8 AUC). Alpha-1-antichymotrypsin (from 108.9 ± 38.6 to 55.5 ± 22.2 ug·mL-1), Creatine Kinase (from 96 ± 34 to 67 ± 23 IU·L-1), general pain, and joint pain decreased in men only, while anxiety and balance (from 0.52 ± 0.13 to 0.45 ± 0.12 cm) improved in women only. Men showed increased performance in vertical jump power (from 2642 ± 244 to 3134 ± 282 W) and grip strength (from 42.1 ± 5.9 to 48.5 ± 4.9 kg).

Conclusions

A multi-nutrient supplement is effective in improving inflammatory status in both men and women, markers of pain, joint pain, strength, and power in men only, and both anxiety and balance (a risk factor for hip fracture) in women. Therefore, a multi-nutrient supplement may help middle-aged individuals to prolong physical function and maintain a healthy, active lifestyle.
Proteomics study of changes in soybean lines resistant and sensitive to Phytophthora sojae
Authors: Zhang YuMei , Zhao JinMing , Xiang Yang , Bian XiaoChun , Zuo QiaoMei , Shen Qi , Gai JunYi , Xing Han
Published: September 2011

Background

Phytophthora sojae causes soybean root and stem rot, resulting in an annual loss of 1-2 billion US dollars in soybean production worldwide. A proteomic technique was used to determine the effects on soybean hypocotyls of infection with P. sojae.

Results

In the present study, 46 differentially expressed proteins were identified in soybean hypocotyls infected with P. sojae, using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight (MALDI-TOF/TOF). The expression levels of 26 proteins were significantly affected at various time points in the tolerant soybean line, Yudou25, (12 up-regulated and 14 down-regulated). In contrast, in the sensitive soybean line, NG6255, only 20 proteins were significantly affected (11 up-regulated and 9 down-regulated). Among these proteins, 26% were related to energy regulation, 15% to protein destination and storage, 11% to defense against disease, 11% to metabolism, 9% to protein synthesis, 4% to secondary metabolism, and 24% were of unknown function.

Conclusion

Our study provides important information on the use of proteomic methods for studying protein regulation during plant-oomycete interactions.
Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids
Authors: Yoshida Takashi , Claverie Jean-Michel , Ogata Hiroyuki
Published: September 2011

Background

The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in bacteria play crucial roles in the metabolism of DNA double-strand breaks, including DNA repair, genome replication, homologous recombination and non-homologous end-joining in cellular life forms and viruses. Here we investigated the amino acid sequence of the Mimivirus R555 gene product, originally annotated as a Rad50 homolog, and later shown to have close homologs in marine microbial metagenomes.

Results

Our bioinformatics analysis revealed that R555 protein sequence is constituted from the fusion of an N-terminal Mre11-like domain with a C-terminal Rad50-like domain. A systematic database search revealed twelve additional cases of Mre11/Rad50 (or SbcD/SbcC) fusions in a wide variety of unrelated organisms including unicellular and multicellular eukaryotes, the megaplasmid of a bacterium associated to deep-sea hydrothermal vents (Deferribacter desulfuricans) and the plasmid of Clostridium kluyveri. We also showed that R555 homologs are abundant in the metagenomes from different aquatic environments and that they most likely belong to aquatic viruses. The observed phyletic distribution of these fusion proteins suggests their recurrent creation and lateral gene transfers across organisms.

Conclusions

The existence of the fused version of protein sequences is consistent with known functional interactions between Mre11 and Rad50, and the gene fusion probably enhanced the opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes in viral metagenomes and their sporadic phyletic distribution in cellular organisms suggest that viruses, plasmids and transposons played a crucial role in the formation of the fusion proteins and their propagation into cellular genomes.
Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells
Authors: Luo Jihuai , Du Junzheng , Gao Shandian , Zhang Guofeng , Sun Jingjing , Cong Guozheng , Shao Junjun , Lin Tong , Chang Huiyun
Published: September 2011

Background

shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV) receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF) and cell enzyme linked immunosorbent assays (cell ELISA), and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells.

Results

Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 106 TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 102 TCID50 of FMDV.

Conclusions

Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.
Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus
Authors: Sand Philipp G , Langguth Berthold , Kleinjung Tobias
Published: September 2011

Membrane-stabilizing drugs have long been used for the treatment of chronic tinnitus, suggesting an underlying disturbance of sensory excitability due to changes in ion conductance. The present study addresses the potassium channel subunit gene KCNE3 as a potential candidate for tinnitus susceptibility. 288 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE3 open reading frame and in the adjacent region by direct sequencing. Allele frequencies were determined for 11 known variants of which two (F66F and R83H) were polymorphic but were not associated with the disorder. No novel variants were identified and only three carriers of R83H were noted. However, owing to a lack of power, our study can neither rule out effects of KCNE3 on the risk for developing chronic tinnitus, nor can it exclude a role in predicting the severity of tinnitus. More extensive investigations are invited, including tests for possible effects of variation in this ion channel protein on the response to treatment.
Acute abdomen due to spontaneous splenic rupture as the first presentation of lung malignancy: a case report
Authors: Kyriacou Angelos , Arulraj Nolan , Varia Haren
Published: September 2011

Introduction

Spontaneous splenic rupture is well recognized in the context of hematological malignancies (lymphoproliferative and myeloproliferative disorders); a few case reports have also linked solid tumors, such as pancreatic and liver cancer, with the occurrence of spontaneous splenic rupture. This is the first case report of lung cancer as a likely cause of spontaneous splenic rupture.

Case presentation

A 61-year-old Caucasian woman presented to our hospital with non-specific symptoms. She developed an 'acute' abdomen and went into a state of shock within twelve hours of her presentation. She was diagnosed with spontaneous splenic rupture with radiology and following a laparotomy. She made an uneventful recovery postoperatively and was simultaneously found to have a bronchial adenocarcinoma.

Conclusion

Spontaneous splenic rupture is a potentially fatal but often unrecognized cause of acute abdomen. It should be routinely considered in the differential diagnosis of acute ('surgical') abdomen and when present it should be promptly dealt with, most commonly with a laparotomy. Once the diagnosis is confirmed there should be an aggressive drive to identify an underlying etiology; malignancy is the commonest culprit. Solid tumors should be considered as underlying causes despite being less common than hematological neoplasms. This case report demonstrates lung malignancy as an underlying precipitating cause of spontaneous splenic rupture.
Lynch syndrome: barriers to and facilitators of screening and disease management
Authors: Watkins Kathy E , Way Christine Y , Fiander Jacqueline J , Meadus Robert J , Esplen Mary Jane , Green Jane S , Ludlow Valerie C , Etchegary Holly A , Parfrey Patrick S
Published: September 2011

Background

Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing.

Methods

The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management.

Results

Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers.

Conclusions

Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.
2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer
Authors: Azzoli Christopher G. , Temin Sarah , Aliff Timothy , Baker Sherman , Brahmer Julie , Johnson David H. , Laskin Janessa L. , Masters Gregory , Milton Daniel , Nordquist Luke , Pao William , Pfister David G. , Piantadosi Steven , Schiller Joan H. , Smith Reily , Smith Thomas J. , Strawn John R. , Trent David , Giaccone Giuseppe
Published: September 2011

Purpose

An American Society of Clinical Oncology (ASCO) focused update updates a single recommendation (or subset of recommendations) in advance of a regularly scheduled guideline update. This document updates one recommendation of the ASCO Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer (NSCLC) regarding switch maintenance chemotherapy.

Clinical Context

Recent results from phase III clinical trials have demonstrated that in patients with stage IV NSCLC who have received four cycles of first-line chemotherapy and whose disease has not progressed, an immediate switch to alternative, single-agent chemotherapy can extend progression-free survival and, in some cases, overall survival. Because of limitations in the data, delayed treatment with a second-line agent after disease progression is also acceptable.

Recent Data

Seven randomized controlled trials of carboxyaminoimidazole, docetaxel, erlotinib, gefitinib, gemcitabine, and pemetrexed have evaluated outcomes in patients who received an immediate, non–cross resistant alternative therapy (switch maintenance) after first-line therapy.

Recommendation

In patients with stage IV NSCLC, first-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients whose disease is stable but not responding to treatment. Two-drug cytotoxic combinations should be administered for no more than six cycles. For those with stable disease or response after four cycles, immediate treatment with an alternative, single-agent chemotherapy such as pemetrexed in patients with nonsquamous histology, docetaxel in unselected patients, or erlotinib in unselected patients may be considered. Limitations of this data are such that a break from cytotoxic chemotherapy after a fixed course is also acceptable, with initiation of second-line chemotherapy at disease progression.