bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroergonomics
Authors: Parasuraman Raja
Published: May 2011

Neuroergonomics is the study of the human brain in relation to performance at work and other everyday settings. Research using two classes of methods—neuroimaging and molecular genetics—is described in four areas: (a) multitasking and mental workload, (b) human error, (c) neuroadaptive interfaces, and (d) individual differences in cognition. The findings show that theoretical and practical understanding of how humans interact with and use technology can be considerably enriched if we also consider the human brain that makes such activities possible.
Treating Constipation in Palliative Care
Authors: Clark Katherine , Byfieldt N. , Dawe M. , Currow D. C.
Published: May 2011

Opioids are major contributing factors to the problem of constipation in palliative care. Whilst this is without doubt, it remains unclear how much other factors also contribute to the problem. The aim of this audit is to review what other contributing factors are present when methylnaltrexone, the peripheral opioid antagonist is prescribed for constipation. The medical records of people prescribed methylnaltrexone over a four-month period were reviewed to examine certain characteristics of people including the whether the reason for constipation was charted, whether other factors that could contribute to constipation were considered and the effectiveness of methylnaltrexone. Over the study period, 10 people received methylnaltrexone, only 4 of whom had a bowel action less than 24 hours after administration with 3 not having any bowel actions reported 6 days after administration. Whilst all were receiving opioids, the opioids doses were in the moderate range (61-200 mg morphine equivalent). However, all had other factors that could contribute to constipation including impaired functional status and medications with anti-cholinergic effects (mean anti-cholinergic load 4.5). In conclusion, methylnaltrexone is targeted treatment for the management of opioid-induced constipation. However, there is a percentage of people who fail to respond. The impact of other factors on the problem of constipation requires greater clarification.
Peritoneal Catheter Site Metastasis in a Patient With Advanced Ovarian Cancer
Authors: Ramirez Ingrid , Bansal Nisha , Hoffman Mitchel
Published: May 2011

Refractory ascites can significantly reduce quality of life in patients with advanced stage ovarian cancer. Paracentesis is a commonly used procedure for the management of refractory ascites. However, there are potential risks associated with paracentesis such as pain, infection, and injury to intra-abdominal organs. In an effort to decrease the number of serial paracentesis, placement of intraperitoneal catheters has been described for the management of intractable ascites. Here we describe a case of metastasis involving a palliative peritoneal catheter in a patient with recurrent ovarian cancer.
Free-Text Comments
Authors: York Grady S. , Churchman Richard , Woodard Beth , Wainright Charles , Rau-Foster Mary
Published: May 2011

Invitations for free-text comments on surveys provide family members of hospice patients an opportunity to “tell” their story of the hospice experience and caregiver relationships during the last months of life. These comments are a rich source of data for understanding the complex interpersonal relationships that influence patient/family perceptions of both quality of care and quality of life. Analysis of 438 free-text comments provided by 243 hospice family members revealed 5 emergent caregiver relationship themes: knowledge, skills, and abilities; empathy and compassion; trust and acceptance; communication experience and time spent with caregiver. Findings support the value of free-text comments to explain or add depth to quality assessments, modify therapeutic interventions, and identify strategies for process improvement that advance hospice quality of care.
Early to Bed, Early to Rise?
Authors: Malone Susan Kohl
Published: May 2011

Cognition, memory, safety, mental health, and weight are all affected by inadequate sleep. Biological studies indicate significant changes in sleep architecture during adolescence, such as changes in melatonin secretion, and a need for greater total sleep time. Yet, social contexts and cultural values impinge on these changing biological sleep needs making adolescents vulnerable to the dangers of insufficient sleep. Sleep hygiene practices are purported as potential mediating factors between biological sleep needs and the sociocultural context of sleep. The purpose of this literature review is to highlight biological and social factors contributing to insufficient sleep in adolescents, to explore the evidence of several recommended sleep hygiene practices, and to stimulate further research about how adolescents negotiate their shifting biological sleep needs amid increasing social demands.
Predicting Recidivism in Homicide Offenders Using Classification Tree Analysis
Authors: Neuilly Melanie-Angela , Zgoba Kristen M. , Tita George E. , Lee Stephen S.
Published: May 2011

Given the severity of the crime and the lengthy sentences often accompanying convictions, homicide tends to be seen as the culminating event in a criminal career. In an attempt to better understand the types of individuals who commit homicide, many studies have examined the offense history of those convicted of murder and manslaughter. Only recently have researchers begun to realize that in some cases homicide is not an end point in the trajectory of one’s criminal career but rather a potential predictor in a continuing criminal career. Building on existing research, the present study uses a sample of 320 homicide offenders convicted, sentenced, imprisoned, and released in New Jersey from 1990 to 2000 to assess which factors predict future recidivism. We find that classification tree analysis in random forests outperform logistic regressions in classification and prediction of recidivism.
A Comparative Examination of Homicides Perpetrated by Far-Right Extremists
Authors: Gruenewald Jeff
Published: May 2011

The current study comparatively examines homicide events perpetrated by far-right extremists and “average” homicide events in the United States. Recent violence has highlighted the threat that far-right extremists pose to public safety and national security. To date, however, little is known about how such events compare to more common forms of homicide. Drawing from research on homicide, “hate crimes,” and domestic terrorism, this study addresses this gap in the research. Original open-source data on far-right extremist perpetrated homicide are integrated with traditional homicide data to overcome methodological and other substantive obstacles that have precluded the study of this form of violence. A number of similarities and differences across these forms of homicide demonstrate the heterogeneity in the nature of homicide in the United States. Implications for policy makers and law enforcement, as well as the broader study of homicide and domestic extremism, are discussed.
Psychological Empowerment Among Urban Youth
Authors: Ozer Emily J. , Schotland Marieka
Published: May 2011

Although there are an increasing number of youth development programs that aim to empower young people, there is a dearth of psychometrically sound measures that can be used to assess flexible youth-led organizing and participatory research approaches that tackle a wide range of social and community problems. This study developed and tested measures of psychological empowerment (PE) and self-efficacy for research and action among a sample of 439 ethnically diverse adolescents primarily recruited from public high schools in an urban center. Items for the PE measure were generated through an iterative combination of conducting formative research with our target population while also drawing on existing theory and measures in the field. We conducted a confirmatory factor analysis of the PE measure, testing four factors: adolescents’ motivation to influence their school and community settings; participatory behavior; sociopolitical skills; and perceived control. Psychometric analyses for the PE scales and their correlation with adolescents’ report of self-esteem, academic achievement, caring relationships with adults at school, and social support from peers are reported; the implications of the present study for research and practice in the youth development and adolescent psychology field are considered.
Describing different operating regimes of journal-bearing materials by pressure velocity diagrams derived from ring-on-disc model testing
Authors: Grün F , Gódor I , Gärtner W , Eichlseder W
Published: May 2011

The loading capacity of metallic journal-bearing materials is investigated in this study under lubricated conditions using a ring-on-disc test configuration. The materials investigated are AlSn20Cu, AlSn40, SnSb7.5Cu3.5, PbSn18Cu2, and AlSn20Cu-Sputter, mated against polished steel counterparts. The loading capacity for different sliding speeds ranging from 0.14 to 2.82 m/s was determined using seizure test procedure. Microscopic analysis of the tested specimen was carried out and the load limits were plotted in pv-diagrams. The results show that for tribomaterials with a load-bearing matrix, as in AlSn-based materials, an increase in the content of soft phase improves fault tolerance. It also increases the loading capacity at low speeds, where adhesion effects dominate. Materials composed of a soft matrix such as Sn- or Pb-based material possess excellent sliding performance but fail due to thermo-mechanical breakdown.
Tangible interventions: the lived landscapes of contemporary archaeology
Authors: Lazzari Marisa
Published: May 2011

Drawing on the contrasting but mutually informative realities of present-day heritage politics of Argentina and Australia, this article explores the links between different cultural practices of preserving artefacts and the lived experience of the landscape. Central to the argument is that such a domain constitutes a specific form of materiality, a diverse field where social significance arises from a long process of entanglement of people with a lived landscape and the many transactions and durations that shaped it. This is explored through artefacts designed to contain ‘uncomfortable objects’, whose ownership cannot be easily located under Western law. Their second life as heritage results in ambiguous locations and valuations as these artefacts question the legitimacy of the available legal and cultural frameworks for their transferability. Together, the uncomfortable objects and the artefacts that contain them tangibly intervene in contemporary projects and concretize ‘past/present systems’, forming an empirical object constituted by mutually dependent terms of equal importance. Building upon conversations, observations and participation in community activities in both countries, the article argues for incorporating present-day encounters into the heart of archaeological analysis. The article follows the current search for hybrid methodologies to examine the contemporary settings of archaeological practice, yet it does so by insisting that the past is irreducible to present experiences.
Building on Mezirow’s Theory of Transformative Learning: Theorizing the Challenges to Reflection
Authors: Mälkki Kaisu
Published: May 2011

The prevailing theoretical discussion on reflection within adult and higher education focuses on the cognitive and rational dimensions of reflection, at the expense of the emotional and social dimensions. Consequently, the theories deal with the ideals, but leave issues pertaining to the understanding of the prerequisites, challenges, and obstacles of reflection largely unaddressed. This article proposes a theory which sheds light on the nature and the prerequisites of the process of reflection. The theory development was based on analyzing Jack Mezirow’s theory of transformative learning. In order to deepen the understanding of the emotional dimension which was fruitfully yet insufficiently conceptualized within Mezirow’s theory, Antonio Damasio’s neurobiological theory of emotions and consciousness was utilized as a complementary theory. Based on these differing theories, it was possible to construct a theory which conceptualizes the challenges to reflection and opens new directions for further research concerning integrating the cognitive and emotional perspectives.
Governing memory: Justice, reconciliation and outreach at the Extraordinary Chambers in the Courts of Cambodia
Authors: Manning Peter
Published: May 2011

This article explores how devolved outreach work for the Extraordinary Chambers in the Courts of Cambodia works to govern the past as it acts to reshape and reframe potentially ambivalent and conflicting memories of political violence. The article specifically examines an example of outreach targeting a former Khmer Rouge community that has been situated as a key party in Cambodia’s attempts to realize ‘justice’ and ‘reconciliation’. The article analyses the sites and crucibles of memory that outreach work for the court utilizes in licensing a particular reading of Cambodia’s experiences of war and genocide. First, the article shows how museum and memorial sites and technologies produce acquiescent, ambivalent and resistant effects among outreach subjects. Second, the article then considers the consolidation and contestation of memory at a public forum event, noting the ways in which outreach attempts to disarm and reconstitute memorial accounts that conflict with the officially sanctioned reading of Cambodia’s past political violence. Whilst acknowledging the unique characteristics of the case, I argue that it is illustrative of the various ways in which Cambodians might question the legitimacy of the Extraordinary Chambers.
RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia
Authors: Holland Mark , Castro Fernanda V. , Alexander Seema , Smith Duncan , Liu Jizhong , Walker Michael , Bitton Danny , Mulryan Kate , Ashton Garry , Blaylock Morgan , Bagley Steve , Connolly Yvonne , Bridgeman John , Miller Crispin , Krishnan Shekhar , Dempsey Clare , Masurekar Ashish , Stern Peter , Whetton Anthony , Saha Vaskar
Published: May 2011

We developed a murine model of CNS disease to obtain a better understanding of the pathogenesis of CNS involvement in pre-B-cell acute lymphoblastic leukemia (ALL). Semiquantitative proteomic discovery–based approaches identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum toxin substrate 2 (RAC2), among others, in an invasive pre-B-cell line that produced CNS leukemia in NOD-SCID mice. Targeting RAC2 significantly inhibited in vitro invasion and delayed disease onset in mice. Induced expression of RAC2 in cell lines with low/absent expression of AEP and ICAM1 did not result in an invasive phenotype or murine CNS disease. Flow cytometric analysis identified an enriched population of blast cells expressing ICAM1/lymphocyte function associated antigen-1 (LFA-1)/CD70 in the CD10+/CD19+ fraction of bone marrow aspirates obtained from relapsed compared with normal controls and those with primary disease. CD10+/CD19+ fractions obtained from relapsed patients also express RAC2 and give rise to CNS disease in mice. Our data suggest that combinations of processes are involved in the pathogenesis of CNS disease in pre-B-cell ALL, support a model in which CNS disease occurs as a result of external invasion, and suggest that targeting the processes of adhesion and invasion unique to pre-B cells may prevent recurrences within the CNS.
Perforin is a critical physiologic regulator of T-cell activation
Authors: Lykens Jennifer E. , Terrell Catherine E. , Zoller Erin E. , Risma Kimberly , Jordan Michael B.
Published: May 2011

Individuals with impaired perforin-dependent cytotoxic function (Ctx−) develop a fatal inflammatory disorder called hemophagocytic lymphohistiocytosis (HLH). It has been hypothesized that immune hyperactivation during HLH is caused by heightened infection, defective apoptosis/responsiveness of Ctx− lymphocytes, or enhanced antigen presentation. Whereas clinical and experimental data suggest that increased T-cell activation drives HLH, potential abnormalities of T-cell activation have not been well characterized in Ctx− hosts. To define such abnormalities and to test these hypotheses, we assessed in vivo T-cell activation kinetics and viral loads after lymphocytic choriomeningitis virus (LCMV) infection of Ctx− mice. We found that increased T-cell activation occurred early during infection of Ctx− mice, while they had viral burdens that were identical to those of WT animals, demonstrating that T-cell hyperactivation was independent of viral load. Furthermore, cell transfer and signaling studies indicated that increased antigenic stimulation, not a cell-intrinsic defect of responsiveness, underlay heightened T-cell activation in vivo. Finally, direct measurement of viral antigen presentation demonstrated an increase in Ctx− mice that was proportional to abnormal T-cell activation. We conclude that perforin-dependent cytotoxicity has an immunoregulatory role that is distinguishable from its pathogen clearance function and limits T-cell activation in the physiologic context by suppressing antigen presentation.
Administration of probiotics influences F4 (K88)-positive enterotoxigenic Escherichia coli attachment and intestinal cytokine expression in weaned pigs
Authors: Daudelin Jean-François , Lessard Martin , Beaudoin Frédéric , Nadeau Éric , Bissonnette Nathalie , Boutin Yvan , Brousseau Jean-Philippe , Lauzon Karoline , Fairbrother John Morris
Published: May 2011

This study evaluated the effect of the probiotics Pediococcus acidilactici and Saccharomyces cerevisiae boulardii on the intestinal colonization of O149 enterotoxigenic Escherichia coli harbouring the F4 (K88) fimbriae (ETEC F4) and on the expression of ileal cytokines in weaned pigs. At birth, different litters of pigs were randomly assigned to one of the following treatments: 1) control without antibiotics or probiotics (CTRL); 2) reference group in which chlortetracycline and tiamulin were added to weanling feed (ATB); 3) P. acidilactici; 4) S. cerevisiae boulardii; or 5) P. acidilactici + S. cerevisiae boulardii. Probiotics were administered daily (1 × 109 CFU per pig) during the lactation period and after weaning (day 21). At 28 days of age, all pigs were orally challenged with an ETEC F4 strain, and a necropsy was performed 24 h later. Intestinal segments were collected to evaluate bacterial colonization in the small intestine and ileal cytokine expressions. Attachment of ETEC F4 to the intestinal mucosa was significantly reduced in pigs treated with P. acidilactici or S. cerevisiae boulardii in comparison with the ATB group (P = 0.01 and P = 0.03, respectively). In addition, proinflammatory cytokines, such as IL-6, were upregulated in ETEC F4 challenged pigs treated with P. acidilactici alone or in combination with S. cerevisiae boulardii compared with the CTRL group. In conclusion, the administration of P. acidilactici or S. cerevisiae boulardii was effective in reducing ETEC F4 attachment to the ileal mucosa, whereas the presence of P. acidilactici was required to modulate the expression of intestinal inflammatory cytokines in pigs challenged with ETEC F4.
Role of redox environment on the oligomerization of higher molecular weight adiponectin
Authors: Briggs David B , Giron Rebecca M , Malinowski Pamela R , Nuñez Martha , Tsao Tsu-Shuen
Published: May 2011

Background

Adiponectin is an adipocyte-secreted hormone with insulin-sensitizing and anti-inflammatory actions. The assembly of trimeric, hexameric, and higher molecular weight (HMW) species of adiponectin is a topic of significant interest because physiological actions of adiponectin are oligomer-specific. In addition, adiponectin assembly is an example of oxidative oligomerization of multi-subunit protein complexes in endoplasmic reticulum (ER).

Results

We previously reported that trimers assemble into HMW adiponectin via intermediates stabilized by disulfide bonds, and complete oxidation of available cysteines locks adiponectin in hexameric conformation. In this study, we examined the effects of redox environment on the rate of oligomer formation and the distribution of oligomers. Reassembly of adiponectin under oxidizing conditions accelerated disulfide bonding but favored formation of hexamers over the HMW species. Increased ratios of HMW to hexameric adiponectin could be achieved rapidly under oxidizing conditions by promoting disulfide rearrangement.

Conclusions

Based upon these observations, we propose oxidative assembly of multi-subunit adiponectin complexes in a defined and stable redox environment is favored under oxidizing conditions coupled with high rates of disulfide rearrangement.
The zebrafish transcriptome during early development
Authors: Vesterlund Liselotte , Jiao Hong , Unneberg Per , Hovatta Outi , Kere Juha
Published: May 2011

Background

The transition from fertilized egg to embryo is accompanied by a multitude of changes in gene expression, and the transcriptional events that underlie these processes have not yet been fully characterized. In this study RNA-Seq is used to compare the transcription profiles of four early developmental stages in zebrafish (Danio rerio) on a global scale.

Results

An average of 79 M total reads were detected from the different stages. Out of the total number of reads 65% - 73% reads were successfully mapped and 36% - 44% out of those were uniquely mapped. The total number of detected unique gene transcripts was 11187, of which 10096 were present at 1-cell stage. The largest number of common transcripts was observed between 1-cell stage and 16-cell stage. An enrichment of gene transcripts with molecular functions of DNA binding, protein folding and processing as well as metal ion binding was observed with progression of development. The sequence data (accession number ERP000635) is available at the European Nucleotide Archive.

Conclusion

Clustering of expression profiles shows that a majority of the detected gene transcripts are present at steady levels, and thus a minority of the gene transcripts clusters as increasing or decreasing in expression over the four investigated developmental stages. The three earliest developmental stages were similar when comparing highly expressed genes, whereas the 50% epiboly stage differed from the other three stages in the identity of highly expressed genes, number of uniquely expressed genes and enrichment of GO molecular functions. Taken together, these observations indicate a major transition in gene regulation and transcriptional activity taking place between the 512-cell and 50% epiboly stages, in accordance with previous studies.
Modeling the asymmetric evolution of a mouse and rat-specific microRNA gene cluster intron 10 of the Sfmbt2 gene
Authors: Lehnert Stefan , Kapitonov Vladimir , Thilakarathne Pushpike J , Schuit Frans C
Published: May 2011

Background

The total number of miRNA genes in a genome, expression of which is responsible for the miRNA repertoire of an organism, is not precisely known. Moreover, the question of how new miRNA genes arise during evolution is incompletely understood. Recent data in humans and opossum indicate that retrotranspons of the class of short interspersed nuclear elements have contributed to the growth of microRNA gene clusters.

Method

We studied a large miRNA gene cluster in intron 10 of the mouse Sfmbt2 gene using bioinformatic tools.

Results

Mice and rats are unique to harbor a 55-65 Kb DNA sequence in intron 10 of the Sfmbt2 gene. This intronic region is rich in regularly repeated B1 retrotransposons together with inverted self-complementary CA/TG microsatellites. The smallest repeats unit, called MSHORT1 in the mouse, was duplicated 9 times in a tandem head-to-tail array to form 2.5 Kb MLONG1 units. The center of the mouse miRNA gene cluster consists of 13 copies of MLONG1. BLAST analysis of MSHORT1 in the mouse shows that the repeat unit is unique for intron 10 of the Sfmbt2 gene and suggest a dual phase model for growth of the miRNA gene cluster: arrangment of 10 MSHORT1 units into MLONG1 and further duplication of 13 head-to-tail MLONG1 units in the center of the miRNA gene cluster. Rats have a similar arrangment of repeat units in intron 10 of the Sfmbt2 gene. The discrepancy between 65 miRNA genes in the mouse cluster as compared to only 1 miRNA gene in the corresponding rat repeat cluster is ascribed to sequence differences between MSHORT1 and RSHORT1 that result in lateral-shifted, less-stable miRNA precursor hairpins for RSHORT1.

Conclusion

Our data provides new evidence for the emerging concept that lineage-specific retroposons have played an important role in the birth of new miRNA genes during evolution. The large difference in the number of miRNA genes in two closely related species (65 versus 1, mice versus rats) indicates that this species-specific evolution can be a rapid process.
Web-based computer adaptive assessment of individual perceptions of job satisfaction for hospital workplace employees
Authors: Chien Tsair-Wei , Lai Wen-Pin , Lu Chih-Wei , Wang Weng-Chung , Chen Shih-Chung , Wang Hsien-Yi , Su Shih-Bin
Published: May 2011

Background

To develop a web-based computer adaptive testing (CAT) application for efficiently collecting data regarding workers' perceptions of job satisfaction, we examined whether a 37-item Job Content Questionnaire (JCQ-37) could evaluate the job satisfaction of individual employees as a single construct.

Methods

The JCQ-37 makes data collection via CAT on the internet easy, viable and fast. A Rasch rating scale model was applied to analyze data from 300 randomly selected hospital employees who participated in job-satisfaction surveys in 2008 and 2009 via non-adaptive and computer-adaptive testing, respectively.

Results

Of the 37 items on the questionnaire, 24 items fit the model fairly well. Person-separation reliability for the 2008 surveys was 0.88. Measures from both years and item-8 job satisfaction for groups were successfully evaluated through item-by-item analyses by using t-test. Workers aged 26 - 35 felt that job satisfaction was significantly worse in 2009 than in 2008.

Conclusions

A Web-CAT developed in the present paper was shown to be more efficient than traditional computer-based or pen-and-paper assessments at collecting data regarding workers' perceptions of job content.
Duration of viral shedding in hospitalized patients infected with pandemic H1N1
Authors: Meschi Silvia , Selleri Marina , Lalle Eleonora , Bordi Licia , Valli Maria B , Ferraro Federica , Ippolito Giuseppe , Petrosillo Nicola , Lauria Francesco N , Capobianchi Maria R
Published: May 2011

Background

The first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm.

Methods

An observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information.

Results

Eleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding.

Conclusions

Our results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.
Histoplasmosis infection in patients with rheumatoid arthritis, 1998-2009
Authors: Olson Timothy C , Bongartz Tim , Crowson Cynthia S , Roberts Glenn D , Orenstein Robert , Matteson Eric L
Published: May 2011

Background

Patients with rheumatic diseases including rheumatoid arthritis (RA) are at increased risk for infections related to both the disease and its treatments. These include uncommonly reported infections due to histoplasmosis.

Methods

Medical record review of all patients with a diagnosis of RA who developed new histoplasmosis infection in an endemic region between Jan 1, 1998 and Jan 30, 2009 and who were seen at Mayo Clinic in Rochester, Minnesota was performed.

Results

Histoplasmosis was diagnosed in 26 patients. Most patients were on combination therapies; 15 were on anti-tumor necrosis factor (anti-TNF) agents, 15 on corticosteroids and 16 on methotrexate. Most received more than 6 months of itraconazole and/or amphotericin treatment. Two patients died of causes unrelated to histoplasmosis. Anti-TNF treatment was restarted in 4/15 patients, with recurrence of histoplasmosis in one.

Conclusions

In this largest single center series of patients with RA and histoplasmosis in the era of immunomodulatory therapy, we found that most patients had longstanding disease and were on multiple immunomodulatory agents. Most cases were pulmonary; typical signs and symptoms of disease were frequently lacking.
Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder
Authors: Lung For-Wey , Tzeng Dong-Sheng , Huang Mei-Feng , Lee Ming-Been
Published: May 2011

Background

The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls.

Methods

Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared.

Results

The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p < 0.001; β = 0.15, p = 0.026; β = 1.11, p < 0.001). Structural equation modeling (SEM) showed that nongenetic factors, such as age, paternal overprotection, and somatic symptoms, were associated with MDD, whereas depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group.

Conclusion

The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.
Military veteran mortality following a survived suicide attempt
Authors: Weiner Janet , Richmond Therese S , Conigliaro Joseph , Wiebe Douglas J
Published: May 2011

Background

Suicide is a global public health problem. Recently in the U.S., much attention has been given to preventing suicide and other premature mortality in veterans returning from Iraq and Afghanistan. A strong predictor of suicide is a past suicide attempt, and suicide attempters have multiple physical and mental comorbidities that put them at risk for additional causes of death. We examined mortality among U.S. military veterans after hospitalization for attempted suicide.

Methods

A retrospective cohort study was conducted with all military veterans receiving inpatient treatment during 1993-1998 at United States Veterans Affairs (VA) medical facilities following a suicide attempt. Deaths occurring during 1993-2002, the most recent available year at the time, were identified through VA Beneficiary and Records Locator System data and National Death Index data. Mortality data for the general U.S. adult population were also obtained from the National Center for Health Statistics. Comparisons within the veteran cohort, between genders, and against the U.S. population were conducted with descriptive statistics and standardized mortality ratios. The actuarial method was used estimate the proportion of veterans in the cohort we expect would have survived through 2002 had they experienced the same rate of death that occurred over the study period in the U.S. population having the age and sex characteristics.

Results

During 1993-1998, 10,163 veterans were treated and discharged at a VA medical center after a suicide attempt (mean age = 44 years; 91% male). There was a high prevalence of diagnosed alcohol disorder or abuse (31.8%), drug dependence or abuse (21.8%), psychoses (21.2%), depression (18.5%), and hypertension (14.2%). A total of 1,836 (18.1%) veterans died during follow up (2,941.4/100,000 person years). The cumulative survival probability after 10 years was 78.0% (95% CI = 72.9, 83.1). Hence the 10-year cumulative mortality risk was 22.0%, which was 3.0 times greater than expected. The leading causes overall were heart disease (20.2%), suicide (13.1%), and unintentional injury (12.7%). Whereas suicide was the ninth leading cause of death in the U.S. population overall (1.8%) during the study period, suicide was the leading and second leading cause among women (25.0%) and men (12.7%) in the cohort, respectively.

Conclusions

Veterans who have attempted suicide face elevated risks of all-cause mortality with suicide being prominent. This represents an important population for prevention activities.
Association of increased plasma adipocyte fatty acid-binding protein with coronary artery disease in non-elderly men
Authors: Doi Masayuki , Miyoshi Toru , Hirohata Satoshi , Nakamura Kazufumi , Usui Shinichi , Takeda Ko , Iwamoto Mutsumi , Kusachi Shozo , Kusano Kengo , Ito Hiroshi
Published: May 2011

Background

Adipocyte fatty acid-binding protein (A-FABP) has been reported to play critical roles in the development of atherosclerosis. We investigated whether an increased in plasma A-FABP level can be independently associated with the presence of coronary artery disease (CAD).

Methods

Two hundred eleven consecutive male patients (mean age: 66 years, range: 33-87 years) were enrolled from inpatients who underwent coronary angiography. Age-matched male subjects (n = 211) having no evidence of CAD served as controls. Plasma A-FABP levels were measured by enzyme-linked immunosorbent assays.

Results

Plasma A-FABP levels in CAD patients were significantly higher than in control subjects (median [IQR], 20.6 [15.7-27.8] ng/mL vs. 15.1 [11.7-19.9] ng/mL, p < 0.01). Multivariate logistic regression analysis revealed that an increased plasma A-FABP level was independently associated with the presence of CAD in all subjects (adjusted odds ratio: 1.76, 95% confidence interval: 1.14 to 2.70, p = 0.01). Furthermore, sub-analysis based on age showed that this association remained significant in subjects aged < 65 years (adjusted odds ratio: 3.06, 95% confidence interval: 1.34 to 6.98, p < 0.01), but not in subjects aged ≥65 years.

Conclusions

Increased plasma A-FABP in non-elderly men had a significant association with the presence of CAD, independent of established CAD risk factors.
The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership
Authors: Lacaze Catherine , Kauss Tina , Kiechel Jean-René , Caminiti Antonella , Fawaz Fawaz , Terrassin Laurent , Cuart Sylvie , Grislain Luc , Navaratnam Visweswaran , Ghezzoul Bellabes , Gaudin Karen , White Nick J , Olliaro Piero L , Millet Pascal
Published: May 2011

Background

Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries.

Methods

Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DNDi).

Results

The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DNDi.

Conclusions

Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under the names of Coarsucam® and Artesunate amodiaquine Winthrop®, Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed.
On-chip constructive cell-Network study (I): Contribution of cardiac fibroblasts to cardiomyocyte beating synchronization and community effect
Authors: Kaneko Tomoyuki , Nomura Fumimasa , Yasuda Kenji
Published: May 2011

Backgrounds

To clarify the role of cardiac fibroblasts in beating synchronization, we have made simple lined-up cardiomyocyte-fibroblast network model in an on-chip single-cell-based cultivation system.

Results

The synchronization phenomenon of two cardiomyocyte networks connected by fibroblasts showed (1) propagation velocity of electrophysiological signals decreased a magnitude depending on the increasing number of fibroblasts, not the lengths of fibroblasts; (2) fluctuation of interbeat intervals of the synchronized two cardiomyocyte network connected by fibroblasts did not always decreased, and was opposite from homogeneous cardiomyocyte networks; and (3) the synchronized cardiomyocytes connected by fibroblasts sometimes loses their synchronized condition and recovered to synchronized condition, in which the length of asynchronized period was shorter less than 30 beats and was independent to their cultivation time, whereas the length of synchronized period increased according to cultivation time.

Conclusions

The results indicated that fibroblasts can connect cardiomyocytes electrically but do not significantly enhance and contribute to beating interval stability and synchronization. This might also mean that an increase in the number of fibroblasts in heart tissue reduces the cardiomyocyte 'community effect', which enhances synchronization and stability of their beating rhythms.
Participation of the oviductal s100 calcium binding protein G in the genomic effect of estradiol that accelerates oviductal embryo transport in mated rats
Authors: Ríos Mariana , Parada-Bustamante Alexis , Velásquez Luis A , Croxatto Horacio B , Orihuela Pedro A
Published: May 2011

Background

Mating changes the mechanism by which E2 regulates oviductal egg transport, from a non-genomic to a genomic mode. Previously, we found that E2 increased the expression of several genes in the oviduct of mated rats, but not in unmated rats. Among the transcripts that increased its level by E2 only in mated rats was the one coding for an s100 calcium binding protein G (s100 g) whose functional role in the oviduct is unknown.

Methods

Herein, we investigated the participation of s100 g on the E2 genomic effect that accelerates oviductal transport in mated rats. Thus, we determined the effect of E2 on the mRNA and protein level of s100 g in the oviduct of mated and unmated rats. Then, we explored the effect of E2 on egg transport in unmated and mated rats under conditions in which s100 g protein was knockdown in the oviduct by a morpholino oligonucleotide against s100 g (s100 g-MO). In addition, the localization of s100 g in the oviduct of mated and unmated rats following treatment with E2 was also examined.

Results

Expression of s100 g mRNA progressively increased at 3-24 h after E2 treatment in the oviduct of mated rats while in unmated rats s100 g increased only at 12 and 24 hours. Oviductal s100 g protein increased 6 h following E2 and continued elevated at 12 and 24 h in mated rats, whereas in unmated rats s100 g protein increased at the same time points as its transcript. Administration of a morpholino oligonucleotide against s100 g transcript blocked the effect of E2 on egg transport in mated, but not in unmated rats. Finally, immunoreactivity of s100 g was observed only in epithelial cells of the oviducts of mated and unmated rats and it was unchanged after E2 treatment.

Conclusions

Mating affects the kinetic of E2-induced expression of s100 g although it not changed the cellular localization of s100 g in the oviduct after E2 . On the other hand, s100 g is a functional component of E2 genomic effect that accelerates egg transport. These findings show a physiological involvement of s100 g in the rat oviduct.
Metallic nano-structures for polarization-independent multi-spectral filters
Authors: Tang Yongan , Vlahovic Branislav , Brady David Jones
Published: May 2011

Cross-shaped-hole arrays (CSHAs) are selected for diminishing the polarization-dependent transmission differences of incident plane waves. We investigate the light transmission spectrum of the CSHAs in a thin gold film over a wide range of features. It is observed that two well-separated and high transmission efficiency peaks could be obtained by designing the parameters in the CSHAs for both p-polarized and s-polarized waves; and a nice transmission band-pass is also observed by specific parameters of a CSHA too. It implicates the possibility to obtain a desired polarization-independent transmission spectrum from the CSHAs by designing their parameters. These findings provide potential applications of the metallic nano-structures in optical filters, optical band-pass, optical imaging, optical sensing, and biosensors.
The Regulation of Leptin, Leptin Receptor and Pro-opiomelanocortin Expression by N-3 PUFAs in Diet-Induced Obese Mice Is Not Related to the Methylation of Their Promoters
Authors: Fan Chaonan , Liu Xinli , Shen Wenwen , Deckelbaum Richard J , Qi Kemin
Published: May 2011

Background

The expression of leptin is increased in obesity and inhibited by n-3 polyunsaturated fatty acids (n-3 PUFAs), but the underlying molecular mechanisms have not been firmly established.

Methods

In this study, we investigated the effects of dietary n-3 PUFAs on the methylation of CpG islands in the promoter regions of the leptin, leptin-R and POMC genes, as well as the effects of n-3 PUFA status in early life on the modification of the promoters of these three genes. Male C57 BL/6J mice were fed a high-fat diet with one of four different fat types: sunflower oil (n-3 PUFA deficient), soy oil, fish oil, or a mixture of soy and fish oil (soy:fish oil = 1:1). Two low-fat diets with sunflower oil or soy oil served as controls. Female mice were fed two breeding diets, sunflower oil or a mixture of soy and fish oil (soy:fish oil = 1:1), during pregnancy and lactation to breed new pups.

Results

Compared to mice fed the control diets, the expression of leptin in fat tissue and leptin-R and POMC in the hypothalamus was higher in the diet-induced obesity (DIO) mice, and the n-3 PUFAs in the diets reversed these elevated expression levels. The mean methylation levels of CpG sites in the promoter regions of the leptin and POMC genes showed no difference between the DIO and the control diet groups nor between the n-3 PUFA-containing and -deficient diet groups. For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups. Feeding mice with the n-3 PUFA diet during pregnancy and lactation did not affect CpG methylation in the leptin or POMC promoters.

Conclusions

Our findings indicate that promoter DNA methylation may not be related to the expression of leptin, leptin-R or its related hypothalamic satiety regulator POMC.