bluuebunny/crossref_metadata_2025 huggingface dataset:
Milrinone Use Is Associated With Postoperative Atrial Fibrillation After Cardiac Surgery
Authors: Fleming Gregory A. , Murray Katherine T. , Yu Chang , Byrne John G. , Greelish James P. , Petracek Michael R. , Hoff Steven J. , Ball Stephen K. , Brown Nancy J. , Pretorius Mias
Published: September 2008

Background—

Postoperative atrial fibrillation (AF), a frequent complication after cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF.

Methods and Results—

We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven patients (28.9%) developed AF a mean of 2.9±2.1 days after surgery. Patients who developed AF stayed in the hospital longer (
P
<0.001) and were more likely to die (
P
=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in nonusers;
P
<0.001). Older age (63.4±10.7 versus 56.7±12.3 years;
P
<0.001), hypertension (
P
=0.04), lower preoperative ejection fraction (
P
=0.03), mitral valve surgery (
P
=0.02), right ventricular dysfunction (
P
=0.03), and higher mean pulmonary artery pressure (27.1±9.3 versus 21.8±7.5 mm Hg;
P
=0.001) also were associated with postoperative AF. In multivariable logistic regression, age (
P
<0.001), ejection fraction (
P
=0.02), and milrinone use (odds ratio, 4.86; 95% confidence interval, 2.31 to 10.25;
P
<0.001) independently predicted postoperative AF. When only data from patients with pulmonary artery catheters were analyzed and pulmonary artery pressure was included in the model, age, milrinone use (odds ratio, 4.45; 95% confidence interval, 2.01 to 9.84;
P
<0.001), and higher pulmonary artery pressure (
P
=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF.

Conclusion—

Milrinone use is an independent risk factor for postoperative AF after elective cardiac surgery.
Interaction Among Heme Oxygenase, Nuclear Factor-κB, and Transcription Activating Factors in Cardiac Hypertrophy in Hypertension
Authors: Jadhav Ashok , Torlakovic Emina , Ndisang Joseph Fomusi
Published: September 2008

Deoxycorticosterone acetate–induced hypertension is a volume overload and human primary aldosteronism model characterized by severe cardiac lesions attributed to elevated inflammation, oxidative stress, fibrosis, and hypertrophy. An important cytoprotective pathway that counteracts tissue insults is the heme oxygenase (HO) system. Although the HO-1 gene promoter contains consensus binding sites for proinflammatory/oxidative transcription factors like nuclear factor-κB, activating protein (AP)-1, and AP-2, the effects of HO inducers on these transcription factors in cardiac lesions of deoxycorticosterone acetate hypertension are not fully understood. Hemin therapy normalized systolic blood pressure and markedly reduced the left:right ventricular ratio, left ventricular wall thickness, and left ventricle:body weight ratio, whereas the HO blocker, chromium mesoporphyrin, exacerbated cardiac fibrosis/hypertrophy in deoxycorticosterone acetate–hypertensive rats. The cardioprotection by hemin was accompanied by increased HO-1, HO activity, cGMP, superoxide dismutase, catalase, the total antioxidant capacity alongside the reduction of 8-isoprostane, AP-1, AP-2, nuclear factor-κB, and c-Jun-NH
2
-terminal kinase, whereas chromium mesoporphyrin abolished the hemin effects. Furthermore, hemin therapy attenuated transforming growth factor-β
1
and extracellular matrix proteins like fibronectin and collagen, with a corresponding reduction of histopathologic lesions, including longitudinal/cross-sectional muscle fiber thickness, scarring, muscular hypertrophy, coronary arteriolar thickening, and collagen deposition. The suppression of AP-1, AP-2, nuclear factor-κB, and c-Jun-NH
2
-terminal kinase proinflammatory/oxidative mediators in the left ventricle of hemin-treated animals is a novel observation that may account for cardioprotection in deoxycorticosterone acetate hypertension. By concomitantly upregulating HO activity and cGMP and potentiating the total antioxidant status, hemin therapy reduced hypertension, suppressed oxidative stress, and attenuated extracellular matrix and remodeling proteins, with a reduction of histopathologic lesions that characterize cardiac fibrosis, hypertrophy, and end-stage organ damage.
Effect of Calcium and Vitamin D Supplementation on Blood Pressure
Authors: Margolis Karen L. , Ray Roberta M. , Van Horn Linda , Manson JoAnn E. , Allison Matthew A. , Black Henry R. , Beresford Shirley A.A. , Connelly Stephanie A. , Curb J. David , Grimm Richard H. , Kotchen Theodore A. , Kuller Lewis H. , Wassertheil-Smoller Sylvia , Thomson Cynthia A. , Torner James C.
Published: September 2008

Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Women’s Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: −0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: −0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.
Making the World Safe for Partial Democracy? Questioning the Premises of Democracy Promotion
Authors: Goldsmith Arthur A.
Published: September 2008

Democracy promotion is a favored strategy to advance the cause of world peace, especially in the Greater Middle East, but undifferentiated democracy promotion has two faulty premises. First, all progress toward the establishment of democratic regimes does not necessarily make the global community safer. Second, regime change is not something external actors have the capacity to direct along desired pathways. The first assumption fails to consider the well-documented security problems caused by partial democracies. The second assumption overstates the ability of powerful outsiders to induce transitions to full democracy. These research findings are grounds for cautious and selective democracy promotion, not a blanket approach that is indifferent to the composition of the regimes designated to be reformed and democratized.
Wishful Thinking or Buying Time? The Logic of British Appeasement in the 1930s
Authors: Ripsman Norrin M. , Levy Jack S.
Published: September 2008

Scholars typically define appeasement as a policy of satisfying grievances through one-sided concessions to avoid war for the foreseeable future and, therefore, as an alternative to balancing. They traditionally interpret British appeasement of Adolf Hitler in the 1930s as a naïve attempt to maintain peace with Germany by satisfying his grievances. The standard conceptualization of appeasement and the empirical treatment of the 1930s, however, are theoretically limiting and historically incorrect. Appeasement is a strategy of sustained, asymmetrical concessions with the aim of avoiding war, at least in the short term. There are three distinct variations of appeasement: (1) resolving grievances (to avoid war for the foreseeable future); (2) diffusing secondary threats (to focus on a greater threat); and (3) buying time (to rearm and/or secure allies against the current threat). British appeasement was primarily a strategy of buying time for rearmament against Germany. British leaders understood the Nazi menace and did not expect that appeasement would avoid an eventual war with Germany. They believed that by the time of the Rhineland crisis of 1936 the balance of power had already shifted in Germany's favor, but that British rearmament would work to reverse the balance by the end of the decade. Appeasement was a strategy to delay an expected confrontation with Germany until the military balance was more favorable.
Ten Years of Instability in a Nuclear South Asia
Authors: Kapur S. Paul
Published: September 2008

The tenth anniversary of India's and Pakistan's 1998 nuclear tests enables scholars to revisit the issue of South Asian proliferation with a decade of hindsight. What lessons do the intervening years hold regarding nuclear weapons' impact on South Asian security? Some scholars claim that nuclear weapons had a beneficial effect during this period, helping to stabilize historically volatile Indo-Pakistani relations. Such optimistic analyses of proliferation's regional security impact are mistaken, however. Nuclear weapons have had two destabilizing effects on the South Asian security environment. First, nuclear weapons' ability to shield Pakistan against all-out Indian retaliation, and to attract international attention to Pakistan's dispute with India, encouraged aggressive Pakistani behavior. This, in turn, provoked forceful Indian responses, ranging from large-scale mobilization to limited war. Although the resulting Indo-Pakistani crises did not lead to nuclear or full-scale conventional conflict, such fortunate outcomes were not guaranteed and did not result primarily from nuclear deterrence. Second, these Indo-Pakistani crises led India to adopt a more aggressive conventional military posture toward Pakistan. This development could exacerbate regional security-dilemma dynamics and increase the likelihood of Indo-Pakistani conflict in years to come. Thus nuclear weapons not only destabilized South Asia in the first decade after the nuclear tests; they may damage the regional security environment well into the future.
Impacts of the Madden–Julian Oscillation on Australian Rainfall and Circulation
Authors: Wheeler Matthew C. , Hendon Harry H. , Cleland Sam , Meinke Holger , Donald Alexis
Published: September 2008

Impacts of the Madden–Julian oscillation (MJO) on Australian rainfall and circulation are examined during all four seasons. The authors examine circulation anomalies and a number of different rainfall metrics, each composited contemporaneously for eight MJO phases derived from the real-time multivariate MJO index. Multiple rainfall metrics are examined to allow for greater relevance of the information for applications. The greatest rainfall impact of the MJO occurs in northern Australia in (austral) summer, although in every season rainfall impacts of various magnitude are found in most locations, associated with corresponding circulation anomalies. In northern Australia in all seasons except winter, the rainfall impact is explained by the direct influence of the MJO’s tropical convective anomalies, while in winter a weaker and more localized signal in northern Australia appears to result from the modulation of the trade winds as they impinge upon the eastern coasts, especially in the northeast. In extratropical Australia, on the other hand, the occurrence of enhanced (suppressed) rainfall appears to result from induced upward (downward) motion within remotely forced extratropical lows (highs), and from anomalous low-level northerly (southerly) winds that transport moisture from the tropics. Induction of extratropical rainfall anomalies by remotely forced lows and highs appears to operate mostly in winter, whereas anomalous meridional moisture transport appears to operate mainly in the summer, autumn, and to some extent in the spring.
Observations of Ekman Currents in the Southern Ocean
Authors: Lenn Yueng-Djern , Chereskin Teresa K.
Published: September 2008

Largely zonal winds in the Southern Ocean drive an equatorward Ekman transport that constitutes the shallowest limb of the meridional overturning circulation of the Antarctic Circumpolar Current (ACC). Despite its importance, there have been no direct observations of the open ocean Ekman balance in the Southern Ocean until now. Using high-resolution repeat observations of upper-ocean velocity in Drake Passage, a mean Ekman spiral is resolved and Ekman transport is computed. The mean Ekman currents decay in amplitude and rotate anticyclonically with depth, penetrating to ∼100-m depth, above the base of the annual mean mixed layer at 120 m. The rotation depth scale exceeds the e-folding scale of the speed by about a factor of 3, resulting in a current spiral that is compressed relative to predictions from Ekman theory. Transport estimated from the observed currents is mostly equatorward and in good agreement with the Ekman transport computed from four different gridded wind products. The mean temperature of the Ekman layer is not distinguishable from temperature at the surface. Turbulent eddy viscosities inferred from Ekman theory and a direct estimate of the time-averaged stress were O(102–103) cm2 s−1. The latter calculation results in a profile of eddy viscosity that decreases in magnitude with depth and a time-averaged stress that is not parallel to the time-averaged vertical shear. The compression of the Ekman spiral and the nonparallel shear–stress relation are likely due to time averaging over the cycling of the stratification in response to diurnal buoyancy fluxes, although the action of surface waves and the oceanic response to high-frequency wind variability may also contribute.
Group diversity and group identification: The moderating role of diversity beliefs
Authors: van Dick Rolf , van Knippenberg Daan , Hägele Silvia , Guillaume Yves R.F. , Brodbeck Felix C.
Published: September 2008

Research on diversity in teams and organizations has revealed ambiguous results regarding the effects of group composition on workgroup performance. The categorization—elaboration model (van Knippenberg et al., 2004) accounts for this variety and proposes two different underlying processes. On the one hand diversity may bring about intergroup bias which leads to less group identification, which in turn is followed by more conflict and decreased workgroup performance. On the other hand, the information processing approach proposes positive effects of diversity because of a more elaborate processing of information brought about by a wider pool and variety of perspectives in more diverse groups. We propose that the former process is contingent on individual team members' beliefs that diversity is good or bad for achieving the team's aims. We predict that the relationship between subjective diversity and identification is more positive in ethnically diverse project teams when group members hold beliefs that are pro-diversity. Results of two longitudinal studies involving postgraduate students working in project teams confirm this hypothesis. Analyses further reveal that group identification is positively related to students' desire to stay in their groups and to their information elaboration. Finally, we found evidence for the expected moderated mediation model with indirect effects of subjective diversity on elaboration and the desire to stay, mediated through group identification, moderated by diversity beliefs.
Annexin A2: biology and relevance to the antiphospholipid syndrome
Authors: Cockrell E , Espinola RG , McCrae KR
Published: September 2008

Antiphospholipid antibodies (aPL), the majority of which are directed against β2-glycoprotein I (β2GPI), are associated with an increased incidence of venous and arterial thrombosis. The pathogenesis of antiphospholipid/anti-β2GPI-associated thrombosis has not been defined, and is likely multifactorial. However, accumulating evidence suggests an important role for endothelial cell activation with the acquisition of a procoagulant phenotype by the activated endothelial cell. Previous work demonstrated that endothelial activation by antiphospholipid/anti-β2GPI antibodies is β2GPI-dependent. We extended these observations by defining annexin A2 as an endothelial β2GPI binding site. We also observed that annexin A2 plays a critical role in endothelial cell activation induced by anti-β2GPI antibodies, and others have described direct endothelial activation by anti-annexin A2 antibodies in patients with aPL . Similar findings have been reported using human monocytes, which also express annexin A2. Because annexin A2 is not a transmembrane protein, how binding of β2GPI/anti-β2GPI antibodies, or anti-annexin A2 antibodies, to endothelial annexin A2 causes cellular activation is unknown. Recent studies, however, suggest an important role for the Toll-like receptor family, particularly TLR4. In this article, we review the role of these interactions in the activation of endothelial cells by aPL . The influence of these antibodies on the ability of annexin A2 to enhance t-PA-mediated plasminogen activation is also discussed.
Sentencing Reforms and the War on Drugs
Authors: Hartley Richard D.
Published: September 2008

Sentencing reforms and the war on drugs have greatly changed the landscape of federal sentencing and the composition of the federal prison population. As of 2006, 56% of federal prison inmates were incarcerated for narcotics offenses. The Sentencing Reform Act of 1984, the United States Sentencing Commission Guidelines, and mandatory minimum statutes were all enacted in an attempt to make sentences more proportional, more uniform, and less disparate. More than 35 years have passed since reform began, and still there are questions about whether unwarranted disparities have been eliminated from the system and whether punishments are more proportional and uniform. Another question that has recently surfaced is whether one unitary federal law can produce uniform sentencing practices because of variations that exist at the district level. This research analyzes the decision-making practices of judges for narcotic violations in four districts in the southwestern United States. The purpose of this study is to illustrate that even in districts that have similar types of cases and political agendas regarding narcotics offending, interdistrict variation in the factors that affect sentencing outcomes still exist.
Piezoelectric Energy Harvesting Improvement with Complex Conjugate Impedance Matching
Authors: Brufau-Penella J. , Puig-Vidal M.
Published: September 2008

One way to enhance the efficiency of energy harvesting systems is complex conjugate impedance matching of its electrical impedance. In Piezoelectric energy Harvesting systems the match is done to increment the energy flows from a vibration energy source to an energy storage electrical circuit. In this article, we compare the power generated using the modulus impedance matching with the power generated using the complex conjugate impedance matching. We present the power ratio between both types of matching methods. The novelty of this article consists of a piezoelectric transducer completely adapted with a complex conjugate impedance match. The theory developed is validated on a commercial piezoelectric transducer QP40w from Midé Technology. The transducer model is first identified by means of a system identification step based on a novel two-port Lumped-Electromechanical Model. The QP40w is complex conjugate matched at its fourth resonant mode increasing the generated power by up to 20% more compared with the modulus match.
Using Fractional Derivatives in Joint Control of Hexapod Robots
Authors: Silva Manuel F. , Tenreiro Macahdo J.A. , Barbosa Ramiro S.
Published: September 2008

This article studies several Fractional Order Control algorithms used for joint control of a hexapod robot. Both Padé and series approximations to the fractional derivative are considered for the control algorithm. The walking performance is evaluated through two indices: The mean absolute density of energy used per unit distance travelled, and the control effort. A set of simulation experiments reveals the influence of the different approximations upon the proposed indices. The results show that the fractional proportional and derivative algorithm, implemented using the Padé approximation with a small number of terms, gives the best results.
Power Time Numerical Integration Algorithm for Nonlinear Fractional Differential Equations
Authors: Nasuno Hiroshi , Shimizu Nobuyuki
Published: September 2008

A numerical integration algorithm to solve single-degree-of-freedom nonlinear fractional differential equations (NFDEs) is proposed, by introducing the power time concept and by means of the Newmark-β method one step scheme. An NFDE involving fractional derivatives of the displacement and the displacement squared is solved numerically, using the proposed power time algorithm. The error analysis of the algorithm, and the contribution of the displacement squared fractional derivative term to the solution of NFDE, are also given.
Depression in Tax Office Workers in Istanbul and its Affecting Factors
Authors: Issever Halim , Ozdilli Kursat , Altunkaynak Oguz , Onen Levent , Disci Rian
Published: September 2008

Depression is a highly prevalent disorder that causes much personal distress and difficulties in functioning at home and the workplace. In the workplace, as elsewhere, depression can manifest as a variation in normal mood, as a symptom, as a disorder or as a disease. In this study we aimed to investigate the determining factors that affect the depression state among official workers. Workers from two tax offices were chosen through random sampling from the 62 tax offices in Istanbul. We used a questionnaire form to determine the demographic and socio-economic characteristics and health problems using face to face negotiations with the workers. We used: `Job Satisfaction Scale', `State and Trait Anxiety Inventory', and `Back Depression Inventory'. The results after statistical evaluation showed that the depression state could be regarded as composed of several factors: high trait anxiety scores, discord with co-workers, and low job satisfaction and backache. In conclusion, a reduction of anxiety levels and an increase in job satisfaction should be arranged, it seemed to be useful to decrease workload and to develop the labor divisions in order to enable the individuals to deal with specific jobs. Also, the relationship between the senior staff and the other employees should be improved. The layout of the work place could be re-arranged to remove the workers' musculoskeletal problems (low-back pain, etc.) and their causes. Finally, it is necessary to expand the occupational health service practices.
Individual Leader Development: An Appreciative Inquiry Approach
Authors: Kaye Hart Rama , Conklin Thomas A. , Allen Scott J.
Published: September 2008

The problem and the solution . Leader development, expanding an individual's leadership capacity, may include learning to transform perspectives as one objective.This paper explores how such transformation might be achieved through appreciative inquiry (AI).The authors define AI and transformative learning and articulate a perspective being advanced which highlights the relationship between them. Using two illustrative examples from organizational and educational settings, the authors describe the AI process and propose how the process might be conducted to achieve transformative leader development. Through these examples, they explore the types of affirmative questions that guided participants' conversations and led to commitment to action and shift in perspectives that are important elements of transformative learning.The authors propose that AI may increase a leader's capacity to generate his or her role anew through inner work and an inside-out orientation (Hunt, 1987). They consider ways in which AI can be coupled with other sources of learning, expanding its use beyond a tool for developing organizational leadership capacity through large-systems organizational change to one that is focused on developing individual leader capacity.
Materials viewpoints in bone regenerative medicine: Progress and prospects
Authors: Thian E. S. , Best S. M.
Published: September 2008

Biomedical materials have always been a priority issue in the healthcare sector. In the orthopaedic field, skeletal replacements, in particularly, hips, knees and shoulders, have become a major health concern, affecting both the young and the older population. There is not yet a clear consensus on a generic material for use in bone tissue engineering applications and the search continues for improved biomaterials, providing the potential for long lasting implants which benefit both patients and surgeons. Materials design thus presents an enormous challenge from both the perspectives of selection and processing. The present paper will address the various material categories such as metals, ceramics, polymers and composites currently being used for the treatment of bone fractures. The new research directions and future for bone regenerative medicine will also be discussed.
Chitosan composites for biomedical applications: Status, challenges and perspectives
Authors: Hein S. , Wang K. , Stevens W. F. , Kjems J.
Published: September 2008

Chitosan is a natural cationic copolymer of N-acetyl glucosamine and D-glucosamine, varying in composition, sequence and molecular chain length. Because of its bio- and cyto-compatibility, biodegradability and bioresorbability, chitosan has been investigated for application in various biomedical fields such as drug and gene delivery, tissue engineering, wound healing, and for use in antimicrobial, antiviral and immunoadjuvant strategies. With the rise of nanotechnology, chitosan together with bioactive nanoparticles are fabricated into various bionanocomposites, providing alternatives to new era of regenerative medicine and drug delivery vesicles. The present paper will review the preparations and biomedical applications of such chitosan composites, their current achievements, limitations and future perspectives. In this respect, the effect of chitosan properties on the interaction with nanoparticles and its consequences for applicability of the resulting composites will be discussed.
Biosorption of chitin and chitosan
Authors: Li C. B. , Hein S. , Wang K.
Published: September 2008

As natural aminopolysaccharides, chitin and chitosan show high intrinsic sorption affinity for dyes, metal ions, chiral molecules and several biomacromolecules. They have been extensively investigated as the high selective, low cost and environment friendly adsorbents. The separation performance of chitin and chitosan can be further improved by physical or chemical modifications designed for a specific application. The present article provides a review of the recent progress in the material preparation, experimental methodologies and mechanisms for the biosorption applications of chitin and chitosan, with the focus on the separation of proteins, lipids, lipopolysaccharides (endotoxins) and chiral molecules. The prospects and challenges in those applications are also discussed.
Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3
Authors: Nelson Erik A. , Walker Sarah R. , Kepich Alicia , Gashin Laurie B. , Hideshima Teru , Ikeda Hiroshi , Chauhan Dharminder , Anderson Kenneth C. , Frank David A.
Published: September 2008

Constitutive activation of the transcription factor STAT3 contributes to the pathogenesis of many cancers, including multiple myeloma (MM). Since STAT3 is dispensable in most normal tissue, targeted inhibition of STAT3 is an attractive therapy for patients with these cancers. To identify STAT3 inhibitors, we developed a transcriptionally based assay and screened a library of compounds known to be safe in humans. We found the drug nifuroxazide to be an effective inhibitor of STAT3 function. Nifuroxazide inhibits the constitutive phosphorylation of STAT3 in MM cells by reducing Jak kinase autophosphorylation, and leads to down-regulation of the STAT3 target gene Mcl-1. Nifuroxazide causes a decrease in viability of primary myeloma cells and myeloma cell lines containing STAT3 activation, but not normal peripheral blood mononuclear cells. Although bone marrow stromal cells provide survival signals to myeloma cells, nifuroxazide can overcome this survival advantage. Reflecting the interaction of STAT3 with other cellular pathways, nifuroxazide shows enhanced cytotoxicity when combined with either the histone deacetylase inhibitor depsipeptide or the MEK inhibitor UO126. Therefore, using a mechanistic-based screen, we identified the clinically relevant drug nifuroxazide as a potent inhibitor of STAT signaling that shows cytotoxicity against myeloma cells that depend on STAT3 for survival.
Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology
Authors: Baenziger Stefan , Heikenwalder Mathias , Johansen Pål , Schlaepfer Erika , Hofer Ursula , Miller Regina C. , Diemand Simone , Honda Kenya , Kundig Thomas M. , Aguzzi Adriano , Speck Roberto F.
Published: September 2008

Chronic immune activation is a major cause for progressive immunodeficiency in human immunodeficiency virus type-1 (HIV) infection. The underlying trigger, however, remains largely unknown. HIV single-stranded RNA is a potent immune activator by triggering Toll-like receptor (TLR) 7/8. Thus, we hypothesized that sustained TLR7 triggering induces chronic immune activation and thereby contributes to progressive immunodeficiency. We used the synthetic compound R848 or a mixture of uridine-rich HIV single-stranded (ss) RNA oligonucleotides—both are potent TLR7/8 agonists—to explore the effects of sustained TLR7 triggering on the murine lymphoid system. Sustained TLR7 triggering induced an immunopathology reminiscent of progressive lymphoid destruction in HIV disease; we observed lymphopenia, elevated proinflammatory cytokines, splenomegaly, contracted lymphoid subsets, and lymphoid microarchitecture alteration with reduced marginal zone B-lymphocytes. Upon exposure to inactivated vesiculo-stomatitis virus, antibody production was abolished, although splenic lymphocytes were activated and total IgG was elevated. Our data imply that HIV itself may directly contribute to immune activation and dysfunction by stimulating TLR7. Thus, manipulation of TLR7 signaling may be a potential strategy to reduce chronic hyper-immune activation and, thereby, disease progression in HIV infection.
Critical role of scavenger receptor-BI–expressing bone marrow–derived endothelial progenitor cells in the attenuation of allograft vasculopathy after human apo A-I transfer
Authors: Feng Yingmei , van Eck Miranda , Van Craeyveld Eline , Jacobs Frank , Carlier Vincent , Van Linthout Sophie , Erdel Martin , Tjwa Marc , De Geest Bart
Published: September 2008

Allograft vasculopathy is the leading cause of death in patients with heart transplantation. Accelerated endothelial regeneration mediated by enhanced endothelial progenitor cell (EPC) incorporation may attenuate the development of allograft vasculopathy. We investigated the hypothesis that modulation of EPC biology and attenuation of allograft vasculopathy by increased high-density lipoprotein cholesterol after human apo A-I (AdA-I) transfer requires scavenger receptor (SR)–BI expression in bone marrow–derived EPCs. After AdA-I transfer, the number of circulating EPCs increased 2.0-fold (P < .001) at different time points in C57BL/6 mice transplanted with SR-BI+/+ bone marrow but remained unaltered in mice with SR-BI−/− bone marrow. The effect of high-density lipoprotein on EPC migration in vitro requires signaling via SR-BI and extracellular signal-regulated kinases and is dependent on increased nitric oxide (NO) production in EPCs. Human apo A-I transfer 2 weeks before paratopic artery transplantation reduced intimal area at day 21 3.7-fold (P < .001) in mice with SR-BI+/+ bone marrow but had no effect in mice with SR-BI−/− bone marrow. AdA-I transfer potently stimulated EPC incorporation and accelerated endothelial regeneration in chimeric SR-BI+/+ mice but not in chimeric SR-BI−/− mice. In conclusion, human apo A-I transfer accelerates endothelial regeneration mediated via SR-BI expressing bone marrow–derived EPCs, thereby preventing allograft vasculopathy.
iRefIndex: A consolidated protein interaction database with provenance
Authors: Razick Sabry , Magklaras George , Donaldson Ian M
Published: September 2008

Background

Interaction data for a given protein may be spread across multiple databases. We set out to create a unifying index that would facilitate searching for these data and that would group together redundant interaction data while recording the methods used to perform this grouping.

Results

We present a method to generate a key for a protein interaction record and a key for each participant protein. These keys may be generated by anyone using only the primary sequence of the proteins, their taxonomy identifiers and the Secure Hash Algorithm. Two interaction records will have identical keys if they refer to the same set of identical protein sequences and taxonomy identifiers. We define records with identical keys as a redundant group. Our method required that we map protein database references found in interaction records to current protein sequence records. Operations performed during this mapping are described by a mapping score that may provide valuable feedback to source interaction databases on problematic references that are malformed, deprecated, ambiguous or unfound. Keys for protein participants allow for retrieval of interaction information independent of the protein references used in the original records.

Conclusion

We have applied our method to protein interaction records from BIND, BioGrid, DIP, HPRD, IntAct, MINT, MPact, MPPI and OPHID. The resulting interaction reference index is provided in PSI-MITAB 2.5 format at http://irefindex.uio.no. This index may form the basis of alternative redundant groupings based on gene identifiers or near sequence identity groupings.
Gene conversion and purifying selection of a placenta-specific ERV-V envelope gene during simian evolution
Authors: Kjeldbjerg Anders L , Villesen Palle , Aagaard Lars , Pedersen Finn Skou
Published: September 2008

Background

Most human endogenous retroviruses (HERVs) invaded our genome at least 25 million years ago. The majority of the viral genes are degenerated, since no selection preserves them within the genome. However, a few intact and very old HERV genes exist, and likely are beneficial for the host. We here address evolutionary aspects of two HERV-V envelope genes, ENVV1 and ENVV2, located in tandem and containing a long open reading frame.

Results

The ENVV2 gene is preserved with an intact reading frame during simian evolution, but none of the ENVV genes are found in the prosimian species tested. While we observe many transposon insertions in the gag and pol regions of the ERV-V2 provirus, the ENVV2 genes have escaped transposon crossfire in all species tested. Additional analysis of nucleotide substitutions provides further strong evidence of purifying selection on the ENVV2 gene during primate evolution. The other copy, ENVV1, seems to be involved in gene conversion of the major part of the envelope. Furthermore, ENVV1 and ENVV2 show placenta-specific expression in human and a baboon species.

Conclusion

Our analyses show that ERV-V entered our genome after the split between simian and prosimian primates. Subsequent purifying selection and gene conversion have preserved two copies of the ENVV envelope gene in most species. This is the first case of gene conversion involving long open reading frames in HERVs. Together with the placenta-specific expression of the human and baboon ENVV1 and ENVV2 envelope genes, these data provide strong evidence of a beneficial role for the host.
Host immunity in the protective response to vaccination with heat-killed Burkholderia mallei
Authors: Whitlock Gregory C , Lukaszewski Roman A , Judy Barbara M , Paessler Slobodan , Torres Alfredo G , Estes D Mark
Published: September 2008

Background

We performed initial cell, cytokine and complement depletion studies to investigate the possible role of these effectors in response to vaccination with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of infection.

Results

While protection with heat-killed bacilli did not result in sterilizing immunity, limited protection was afforded against an otherwise lethal infection and provided insight into potential host protective mechanisms. Our results demonstrated that mice depleted of either B cells, TNF-α or IFN-γ exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route. Additionally, complement depletion had no effect on immunoglobulin production when compared to non-complement depleted controls infected intranasally.

Conclusion

The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model. The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-γ and TNF-α in protection following HK vaccination.
Is there a need for a GP consultant at a university hospital?
Authors: Mulder J , Groenier KH , Dekker JH , Berendsen AJ , Schuling J
Published: September 2008

Background

Patients in hospital can develop complaints unrelated to the condition they are admitted for. The treating specialist will then call upon a co-specialist who is specialized in the clinical picture associated with the new complaint. For such a complaint, the GP is usually the first contact, when the patient is not in hospital. Normally specialists only encounter patients GPs have selected for referral. The risk of the specialist overestimating the predictive value of 'unselected' complaints and symptoms of a serious condition is high. This may lead to an overuse of diagnostic treatments. Such treatments weigh more heavily on the patient, cause inadequate use of hospital facilities and, as a consequence, generate higher costs.

Because of these considerations, we wished to investigate if there is a need for the GP as a consultant for new complaints during hospital admittance.

Method

The files of a random sample of patients who had an interdisciplinary consultation during their stay in hospital were judged by an expertpanel whether the consultation fitted the expertise of a GP.

Results

In 28 out of 84 files the consultation fitted the expertise of a GP; most cases concerned a specific condition that is not part of the specialist's expertise, most frequently dermatological problems. In a minority of cases the specialist is confronted with a clinical problem with symptoms of which the cause is not clear, for example fever.

Conclusion

Generally, the consultations concern serious, often very complex conditions, i.e. cases that should be assessed by a specialist. Nevertheless, the expert panel's judgment of the interdisciplinary consultations shows that in more than half of the dermatological cases and in a limited number of consultations by a specialist of internal medicine and geriatrics the problems fit the GP's expertise.

Given the morbidity in academic hospitals we suppose that the results of a similar study in a peripheral hospital might even show more perspective for a GP consultant. These results offer sufficient arguments to start a pilotstudy into the role of a GP consultant in hospital.
Chinese journals: a guide for epidemiologists
Authors: Fung Isaac CH
Published: September 2008

Chinese journals in epidemiology, preventive medicine and public health contain much that is of potential international interest. However, few non-Chinese speakers are acquainted with this literature. This article therefore provides an overview of the contemporary scene in Chinese biomedical journal publication, Chinese bibliographic databases and Chinese journals in epidemiology, preventive medicine and public health. The challenge of switching to English as the medium of publication, the development of publishing bibliometric data from Chinese databases, the prospect of an Open Access publication model in China, the issue of language bias in literature reviews and the quality of Chinese journals are discussed. Epidemiologists are encouraged to search the Chinese bibliographic databases for Chinese journal articles.
Enhancement of Presynaptic Glutamate Release and Persistent Inflammatory Pain by Increasing Neuronal cAMP in the Anterior Cingulate Cortex
Authors: Wu Long-Jun , Steenland Hendrik W , Kim Susan S , Isiegas Carolina , Abel Ted , Kaang Bong-Kiun , Zhuo Min
Published: September 2008

Both presynaptic and postsynaptic alterations are associated with plastic changes of brain circuits, such as learning and memory, drug addiction and chronic pain. However, the dissection of the relative contributions of pre- and postsynaptic components to brain functions is difficult. We have previously shown peripheral inflammation caused both presynaptic and postsynaptic changes and calcium-stimulated cyclic AMP (cAMP) pathway in the anterior cingulate cortex (ACC) is critical in the synaptic plasticity and behavioral sensitization to pain. It remains to be elucidated whether presynaptic or postsynaptic modulation by cAMP in the ACC could be sufficient for enhancing inflammatory pain. In order to address this question, we took advantage of a novel transgenic mouse model, heterologously expressing an Aplysia octopamine receptor (Ap oa1). This receptor is G protein-coupled and selectively activates the cAMP pathway. We found that activation of Ap oa1 by octopamine enhanced glutamatergic synaptic transmission in the ACC by increasing presynaptic glutamate release in vitro. Bilateral microinjection of octopamine into the ACC significantly facilitated behavioral responses to inflammatory pain but not acute pain. The present study provides the first evidence linking enhanced presynaptic glutamate release in the ACC to behavioral sensitization caused by peripheral inflammation.
Emphysematous pyelonephritis in type II diabetes: A case report of an undiagnosed ureteric colic
Authors: Vollans Samuel R , Sehjal Ranjit , Forster James A , Rogawski Karol M
Published: September 2008

Introduction

Emphysematous pyelonephritis (EPN) is a severe acute necrotising infection of the renal parenchyma and perirenal tissue, characterised by gas formation. 90% of cases are seen in association with diabetes mellitus. We report a case of undiagnosed ureteric obstruction in a type II diabetic, leading to EPN requiring emergency nephrectomy.

Case presentation

A 59-year-old type II tablet controlled diabetic woman presented complaining of a five day history of right sided abdominal pain associated with vomiting, abdominal distension and absolute constipation. There were no lower urinary tract symptoms. Past surgical history included an open appendectomy and an abdominal hysterectomy. On examination, she was haemodynamically stable, the abdomen was soft, distended, and tender in the right upper and lower quadrants with no bowel sounds. Investigations revealed a CRP of 365 and 2+ blood and nitrite positive on the urine dipstick. The AXR was reported as normal on admission, however when reviewed in retrospect revealed the diagnosis. She was managed, therefore, as having adhesional bowel obstruction and a simple UTI. After four days, a CT was organised as she was not settling. This showed a right pyohydronephrosis with gas in the collecting system secondary to an 8 mm obstructing ureteric calculus. The kidney was drained percutaneously via a nephrostomy and the patient was commenced on a broad spectrum intravenous antibiotics. Despite this, she went on to need an emergency nephrectomy for uncontrolled severe sepsis. She was discharged in good health 15 days later.

Conclusion

EPN carries a mortality of up to 40% with medical management alone. Early recognition of EPN in an obstructed kidney is essential to guide aggressive management, and in the presence of continued severe sepsis or organ dysfunction an urgent nephrectomy should be carried out. Diabetic patients who are known to have renal or ureteric calculi, whether symptomatic or not, should be considered for percutanous or ureteroscopic treatment. In the acute abdomen, the plain abdominal radiograph should always be viewed with respect to general surgical, vascular and urological differential diagnoses.
Cognitive markers of short-term clinical outcome in first-episode psychosis
Authors: Bodnar Michael , Malla Ashok , Joober Ridha , Lepage Martin
Published: September 2008

Background

Outcome from psychotic disorders is heterogeneous with poorer outcomes frequently identified too late to be influenced. Symptomatic ratings at 1 or more years following initiation of treatment have been related to cognition in firstepisode psychosis. However, the relationship between cognition and early outcome remains unclear.

Aims

To determine whether specific cognitive domains could identify poor short-term outcome among individuals with first-episode psychosis.

Method

One hundred and fifty-one individuals with first-episode psychosis were divided into two groups based on 6-month clinical data after the initiation of treatment. Six cognitive domains were compared among 78 participants with poor outcomes, 73 with good outcomes and 31 healthy controls.

Results

Lower performance on verbal memory (z-scores: poor outcome=–1.3 (s.d.=1.1); good outcome=–0.8 (s.d.=0.9);P=0.001) and working memory (poor outcome=–1.0 (s.d.=1.2); good outcome=–0.4 (s.d.=0.9);P=0.003) identified individuals with first-episode psychosis with a poor outcome after 6 months of treatment.

Conclusions

The early identification of those individuals with first-episode psychosis with a poor clinical outcome may encourage clinicians to pay special attention to them in the form of alternative pharmacological and psychological treatments for a more favourable outcome in the long term.
Dedicated community-based services for adults with personality
disorder: Delphi study
Authors: Crawford Mike J. , Price Katy , Rutter Deborah , Moran Paul , Tyrer Peter , Bateman Anthony , Fonagy Peter , Gibson Sarah , Weaver Tim
Published: September 2008

Dedicated community-based services have been recommended for people with
personality disorder, but little is known about how such services should be
configured. We conducted a Delphi survey to assess opinions about this. A
panel of expert authors, service providers and service users agreed on only
21 (39%) of 54 statements on the organisation and delivery of care.
Consensus was not reached on important issues such as working with people
with a history of violent offending, the role of community outreach and the
use of compulsory treatment. Further work needs to be undertaken before the
optimal organisation of dedicated personality disorder services can be
agreed.