bluuebunny/crossref_metadata_2025 huggingface dataset:
Why patient summaries in electronic health records do not provide the cognitive support necessary for nurses’ handoffs on medical and surgical units: Insights from interviews and observations
Authors: Staggers Nancy , Clark Lauren , Blaz Jacquelyn W. , Kapsandoy Seraphine
Published: September 2011

Patient care handoffs are cognitively intense activities, especially on medical and surgical units where nurses synthesize information across an average of four to five patients every shift. The objective of this study was to examine handoffs and nurses’ use of computerized patient summary reports in an electronic health record after computerized provider order entry (CPOE) was installed. We observed and audio taped 93 patient handoffs on 25 occasions on 5 acute care units in 2 different facilities sharing a vendor’s electronic health record. We found that the computerized patient summary report and the electronic health record were minimally used during the handoff and that the existing patient summary reports did not provide adequate cognitive support for nurses. The patient summary reports were incomplete, rigid and did not offer “at a glance” information, or help nurses encode information. We make recommendations about a redesign of patient summary reports and technology to support the cognitive needs of nurses during handoffs at the change of shift.
Defining blog: A fool’s errand or a necessary undertaking
Authors: Garden Mary
Published: September 2011

Weblogs (blogs) emerged as a grassroots phenomenon in the late 1990s and since then their growth has been staggering. There has also been a growing body of scholarship with an underlying assumption that there is consensus about the definition of the word ‘blog’, which there is not. This article reviews some of the varied ways the term is being used, addresses the distinction as to whether a blog should be considered a medium or a genre, and considers whether links and comment-threads are defining characteristics. This article argues that the real problem is not that the term blog is difficult to define (it is) but that most scholars are using it in vague, contradictory, ambiguous and imprecise ways. Definitions require descriptive qualifiers to reflect current usages, and scholars need to provide clear and precise definitions according to the particular research questions asked and the target populations of interest.
Copyrighting Media Labor and Production
Authors: Han Dong
Published: September 2011

This article examines the role of copyright in production and labor relations within media institutions. Specifically, it examines China Central Television’s (CCTV’s) copyright reform and argues that developmental strategies and market conditions may diminish or promote copyright’s role in commercial media. In CCTV’s case, two factors contributed to the insignificance of copyright in the 1990s, namely, the reliance on advertising as the major revenue source and CCTV’s centralized power in the television sector. Yet the circumstances changed in the 2000s with the slowdown of advertising growth, which brought copyright to the forefront of CCTV’s market reform. During the process, the dominating role of CCTV vis-à-vis non-unionized media workers resulted in copyright reform that was slanted toward corporate interests. The implications of the path of CCTV’s copyright reform are highly relevant for understanding media and copyright growth in contemporary China and in other media systems undergoing contested processes of marketization.
The House of Glass Noodles
Authors: Blinne Kristen C.
Published: September 2011

Borrowing the “unreal” to cultivate the “real,” this co-performance fuses fact and fiction as a tool to bring this lived experience to life.
Prognostic Proof and Possible Therapeutic Mechanisms of Herbal Medicine in Patients With Metastatic Lung and Colon Cancer
Authors: Baak Jan P. A. A. , Gyllenhaal Charlotte , Liu Luming , Guo Huiru , Block Keith I.
Published: September 2011

Recent studies based on epidemiological models published in this journal and elsewhere have demonstrated encouraging patterns suggesting that herbal treatment may improve prognosis in advanced colon and lung cancer patients. Various problems exist with data from nonrandomized studies of this type, but a strong signal of potential positive effect can be seen. The therapeutic mechanisms of traditional Chinese medicine in metastatic cancer are discussed against a hypothetical, dualistic antiproliferation model and immune-stimulation model of tumor progression and regression. Recommendations are made for a strategy to demonstrate more conclusively the efficacy of adjunct herbal treatment during cancer chemotherapy and for discussions with patients until such time as the efficacy trials are completed.
AIDS-Related Kaposi's Sarcoma Can Occur during Peginterferon-α and Ribavirin Therapy for Chronic Hepatitis C Infection
Authors: de Lastours Victoire , Pavie Juliette , Delaugerre Constance , Molina Jean-Michel
Published: September 2011

Introduction: Before the arrival of highly active antiretroviral therapy (HAART), interferon α has been used successfully to treat AIDS-related Kaposi's sarcoma (KS). Peginterferon-α (pegIFN-α) may still be used successfully in refractory KS. Case: Peginterferon-α and ribavirin (RBV) were initiated to treat hepatitis C virus (HCV) infection in an HIV-infected patient with high CD4 counts having discontinued antiretroviral therapy (ART). He developed disseminated KS 6 months after HCV treatment began. Beginning of ART, discontinuation of pegIFN/RBV, and 2 cycles of doxorubicine were necessary to treat KS. Discussion: Despite its activity on KS, thanks to its antiviral and antiangiogenic properties, PegIFN was unable to prevent the occurrence of severe KS. The absence of ART, despite high CD4 counts, and interferon-induced lymphopenia probably triggered the occurrence of KS in this patient.
Transgender Day of Remembrance and a Prospective Student Open House
Authors: Fusarelli Bonnie C. , Eaton Lucy E.
Published: September 2011

This case study explores the challenges a school leader faced when her commitment to diversity was tested by a scheduling conflict. The school principal approved a Transgender Day of Remembrance but then realized that it was scheduled for the same night as the school’s Open House to recruit prospective students. The case study provides an opportunity for both practicing and aspiring school leaders to explore a number of dilemmas related to social justice and equity.
My Name Is Michelle
Authors: Boske Christa
Published: September 2011

In this case narrative, Michelle, a young teenage male adolescent considering the transition from male to female, becomes the target of viscous teasing and physical abuse, especially when she does not conform to the school’s gender expectations. As a result, it presents school leaders with a contemporary issue facing lesbian/gay/bisexual/transgender/queer/intersex/ally youth while providing insight regarding the frequency of homophobic comments from students and staff. Unlike the majority of JCEL cases, which portray fictitious administrators facing hypothetical dilemmas, this case is based on a real incident and puts you in the middle of the story—as you take on the role of the assistant principal in the case.
Challenges using online surveys in a Danish population of people with type 2 diabetes
Authors: Schiøtz Michaela , Bøgelund Mette , Willaing Ingrid
Published: September 2011

Objectives: To investigate response rates for online and paper versions of an identical questionnaire and the differences between respondents to each and between respondents and non-respondents among a population with type 2 diabetes.

Methods: We mailed letters containing an invitation to complete an online questionnaire to 2045 individuals, followed by two reminders; the second included a paper version of the questionnaire.

Results: In total, 1081 people responded to either version of the questionnaire, yielding a response rate of 54%. Compared to total respondents, respondents completing the online version were more likely to be male, better educated, and younger, and have had diabetes for a shorter period of time. Compared to non-respondents, respondents were more likely to be male and have a lower hemoglobin A1c level.

Conclusion: Web-based surveys are capable of delivering a substantial number of responses cost-effectively. However, disadvantages related to selection bias should be taken into account, and mixed-mode methods should be considered when surveying populations with type 2 diabetes.
Integrated methodology for evaluation of energy performance of the building enclosures: Part 4 – material characterization for input to hygrothermal models
Authors: Yu Shui , Bomberg Mark , Zhang Xu
Published: September 2011

Reviewing hygrothermal input data published in handbooks such as ASHRAE or ASTM, one often finds large range of variability in hygric properties of construction materials. Two factors that cause variability of these results are uncertainty of the test method and inadequate characterization of the material sample. Adequate characterization of the tested sample, despite being one of the most critical aspects of any material property measurement, is however frequently neglected. Yet, performing a high-precision test when the sample is not adequately characterized does not tell us what material was tested and therefore is not precise.

Typically porous materials are characterized with geometrical properties such as mean pore size and pore-size distribution, but this approach bring as many new questions as it addresses. In this context, a position paper from CIB W40 written almost 10 years ago proposed using critical hygrothermal characteristics for material characterization as well as for the input to the models. Yet, with a few recently completed PhD, revisiting this issue may support the use of hygrothermal models for field performance calculations.
Communicating Governments
Authors: Sanders Karen , Crespo María José Canel , Holtz-Bacha Christina
Published: September 2011

Various studies have attempted to conceptualize and assess professionalization of political communication from different perspectives. This article examines the professionalization of central government communication in Germany, Spain, and the United Kingdom, applying a framework developed using indicators derived from the sociology of work and from the strategic planning and quality literature. Results show that there are clear indices of the development of formal rules governing the practice of policy- or information-related government communication, distinguishing it from more partisan, politicized communication. Although mechanisms are being introduced to improve the process of communication, practices are still far from being fully systematized. The analysis provides evidence that professionalization as indicated by the establishment of specialist education, of self-regulation, and of formal organization of communication processes can be found at varying speeds in the three countries. The article finally discusses whether the logic of professionalism is compatible with government communication that is manipulative.
More Affected = More Neglected
Authors: Sah Sunita , Loewenstein George
Published: September 2011

Professionals often give advice to many anonymous people. For example, financial analysts give public recommendations to trade stock, and medical experts formulate clinical guidelines that affect many patients. Normatively, awareness of the advice-recipient’s identity should not influence the quality of advice, and when advice affects a larger number of people, if anything, greater care should be taken to ensure its accuracy. Yet, contrary to this logic and consistent with research on the identifiable victim effect, results from two experimental studies demonstrate that advisors confronting a financial conflict of interest give more biased advice to multiple than single recipients and to unidentified than identified single recipients. Increased intensity of feelings toward single identified recipients appears to drive this process; advisors experience more empathy and appear to have greater awareness and motivation to reduce bias in their advice when the recipient is single and identified.
Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation
Authors: Lewkowich Ian P , Day Scottie B , Ledford John R , Zhou Ping , Dienger Krista , Wills-Karp Marsha , Page Kristen
Published: September 2011

Background

A common characteristic of allergens is that they contain proteases that can activate protease-activated receptor (PAR-2); however the mechanism by which PAR-2 regulates allergic airway inflammation is unclear.

Methods

Mice (wild type and PAR-2-deficient) were sensitized using German cockroach (GC) feces (frass), the isolated protease from GC frass, or through adoptive transfer of GC frass-treated bone marrow-derived dendritic cells (BMDC) and measurements of airway inflammation (cellular infiltration, cytokine expression, and mucin production), serum IgE levels and airway hyperresponsiveness (AHR) were assessed. BMDC were cultured, treated with GC frass and assessed for cytokine production. PAR-2 expression on pulmonary mDCs was determined by flow cytometry.

Results

Exposure to GC frass induced AHR and airway inflammation in wild type mice; however PAR-2-deficient mice had significantly attenuated responses. To directly investigate the role of the protease, we isolated the protease from GC frass and administered the endotoxin-free protease into the airways of mice in the presence of OVA. GC frass proteases were sufficient to promote the development of AHR, serum IgE, and Th2 cytokine production. PAR-2 expression on mDC was upregulated following GC frass exposure, but the presence of a functional PAR-2 did not alter antigen uptake. To determine if PAR-2 activation led to differential cytokine production, we cultured BMDC in the presence of GM-CSF and treated these cellsex vivowith GC frass. PAR-2-deficient BMDC released significantly less IL-6, IL-23 and TNFα compared to BMDC from wild type mice, suggesting PAR-2 activation was important in Th2/Th17 skewing cytokine production. To determine the role for PAR-2 on mDCs on the initiation of allergic airway inflammation, BMDCs from wild type and PAR-2-deficient mice were treated in the presence or absence of GC frass and then adoptively transferred into the airway of wild type mice. Importantly, GC frass-stimulated wild type BMDCs were sufficient to induce AHR and allergic airway inflammation, while GC frass-stimulated PAR-2-deficient BMDC had attenuated responses.

Conclusions

Together these data suggest an important role for allergen activation of PAR-2 on mDCs in mediating Th2/Th17 cytokine production and allergic airway responses.
Sirtuin-mediated nuclear differentiation and programmed degradation in Tetrahymena
Authors: Slade Kristin M , Freggiaro Sydney , Cottrell Kyle A , Smith Joshua J , Wiley Emily A
Published: September 2011

Background

The NAD+-dependent histone deacetylases, known as "sirtuins", participate in a variety of processes critical for single- and multi-cellular life. Recent studies have elucidated the importance of sirtuin activity in development, aging, and disease; yet, underlying mechanistic pathways are not well understood. Specific sirtuins influence chromatin structure and gene expression, but differences in their pathways as they relate to distinct chromatin functions are just beginning to emerge. To further define the range of global chromatin changes dependent on sirtuins, unique biological features of the ciliated protozoanTetrahymena thermophilacan be exploited. This system offers clear spatial and temporal separation of multiple whole genome restructuring events critical for the life cycle.

Results

Inhibition with nicotinamide revealed that sirtuin deacetylase activity inTetrahymenacells promotes chromatin condensation during meiotic prophase, differentiation of heterochromatin from euchromatin during development, and chromatin condensation/degradation during programmed nuclear death. We identified a class I sirtuin, called Thd14, that resides in mitochondria and nucleoli during vegetative growth, and forms a large sub-nuclear aggregate in response to prolonged cell starvation that may be peripherally associated with nucleoli. During sexual conjugation and development Thd14 selectively concentrates in the parental nucleus prior to its apoptotic-like degradation.

Conclusions

Sirtuin activity is important for several functionally distinct events requiring global chromatin condensation. Our findings suggest a novel role for sirtuins in promoting programmed pycnosis by acting on chromatin destined for degradation. The sirtuin Thd14, which displays physiological-dependent differential localization within the nucleus, is a candidate for a chromatin condensation enzyme that is coupled to nuclear degradation.
Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis
Authors: Turchetto-Zolet Andreia C , Maraschin Felipe S , de Morais Guilherme L , Cagliari Alexandro , Andrade Cláudia MB , Margis-Pinheiro Marcia , Margis Rogerio
Published: September 2011

Background

Triacylglycerides (TAGs) are a class of neutral lipids that represent the most important storage form of energy for eukaryotic cells. DGAT (acyl-CoA: diacylglycerol acyltransferase; EC 2.3.1.20) is a transmembrane enzyme that acts in the final and committed step of TAG synthesis, and it has been proposed to be the rate-limiting enzyme in plant storage lipid accumulation. In fact, two different enzymes identified in several eukaryotic species, DGAT1 and DGAT2, are the main enzymes responsible for TAG synthesis. These enzymes do not share high DNA or protein sequence similarities, and it has been suggested that they play non-redundant roles in different tissues and in some species in TAG synthesis. Despite a number of previous studies on the DGAT1 and DGAT2 genes, which have emphasized their importance as potential obesity treatment targets to increase triacylglycerol accumulation, little is known about their evolutionary timeline in eukaryotes. The goal of this study was to examine the evolutionary relationship of the DGAT1 and DGAT2 genes across eukaryotic organisms in order to infer their origin.

Results

We have conducted a broad survey of fully sequenced genomes, including representatives of Amoebozoa, yeasts, fungi, algae, musses, plants, vertebrate and invertebrate species, for the presence of DGAT1 and DGAT2 gene homologs. We found that the DGAT1 and DGAT2 genes are nearly ubiquitous in eukaryotes and are readily identifiable in all the major eukaryotic groups and genomes examined. Phylogenetic analyses of the DGAT1 and DGAT2 amino acid sequences revealed evolutionary partitioning of the DGAT protein family into two major DGAT1 and DGAT2 clades. Protein secondary structure and hydrophobic-transmembrane analysis also showed differences between these enzymes. The analysis also revealed that the MGAT2 and AWAT genes may have arisen from DGAT2 duplication events.

Conclusions

In this study, we identified several DGAT1 and DGAT2 homologs in eukaryote taxa. Overall, the data show that DGAT1 and DGAT2 are present in most eukaryotic organisms and belong to two different gene families. The phylogenetic and evolutionary analyses revealed that DGAT1 and DGAT2 evolved separately, with functional convergence, despite their wide molecular and structural divergence.
A new high-throughput method for simultaneous detection of drug resistance associated mutations in Plasmodium vivax dhfr, dhps and mdr1 genes
Authors: Barnadas Céline , Kent David , Timinao Lincoln , Iga Jonah , Gray Laurie R , Siba Peter , Mueller Ivo , Thomas Peter J , Zimmerman Peter A
Published: September 2011

Background

Reports of severe cases and increasing levels of drug resistance highlight the importance of improved Plasmodium vivax case management. Whereas monitoring P. vivax resistance to anti-malarial drug by in vivo and in vitro tests remain challenging, molecular markers of resistance represent a valuable tool for high-scale analysis and surveillance studies. A new high-throughput assay for detecting the most relevant markers related to P. vivax drug resistance was developed and assessed on Papua New Guinea (PNG) patient isolates.

Methods

Pvdhfr, pvdhps and pvmdr1 fragments were amplified by multiplex nested PCR. Then, PCR products were processed through an LDR-FMA (ligase detection reaction - fluorescent microsphere assay). 23 SNPs, including pvdhfr 57-58-61 and 173, pvdhps 382-383, 553, 647 and pvmdr1 976, were simultaneously screened in 366 PNG P. vivax samples.

Results

Genotyping was successful in 95.4% of the samples for at least one gene. The coexistence of multiple distinct haplotypes in the parasite population necessitated the introduction of a computer-assisted approach to data analysis. Whereas 73.1% of patients were infected with at least one wild-type genotype at codons 57, 58 and 61 of pvdhfr, a triple mutant genotype was detected in 65.6% of the patients, often associated with the 117T mutation. Only one patient carried the 173L mutation. The mutant 647P pvdhps genotype allele was approaching genetic fixation (99.3%), whereas 35.1% of patients were infected with parasites carrying the pvmdr1 976F mutant allele.

Conclusions

The LDR-FMA described here allows a discriminant genotyping of resistance alleles in the pvdhfr, pvdhps, and pvmdr1 genes and can be used in large-scale surveillance studies.
A MCP1 fusokine with CCR2-specific tumoricidal activity
Authors: Rafei Moutih , Deng Jiusheng , Boivin Marie-Noëlle , Williams Patrick , Matulis Shannon M , Yuan Shala , Birman Elena , Forner Kathy , Yuan Liangping , Castellino Craig , Boise Lawrence H , MacDonald Tobey J , Galipeau Jacques
Published: September 2011

Background

The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development.

Methods

We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76) [hereafter GMME1] and investigated its utility as a CCR2-specific tumoricidal agent.

Results

We found that distinct to full length CCL2 or its N-truncated derivative (CCL2 5-76), GMME1 bound to CCR2 on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up-regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from patients.

Conclusion

Our data demonstrate that GMME1 is a fusokine with a potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be exploited as a novel biological therapy for CCR2+ malignancies including lymphoid and central nervous system malignancies.
Treatment with gelsolin reduces brain inflammation and apoptotic signaling in mice following thermal injury
Authors: Zhang Qing-Hong , Chen Qi , Kang Jia-Rui , Liu Chen , Dong Ning , Zhu Xiao-Mei , Sheng Zhi-Yong , Yao Yong-Ming
Published: September 2011

Background

Burn survivors develop long-term cognitive impairment with increased inflammation and apoptosis in the brain. Gelsolin, an actin-binding protein with capping and severing activities, plays a crucial role in the septic response. We investigated if gelsolin infusion could attenuate neural damage in burned mice.

Methods

Mice with 15% total body surface area burns were injected intravenously with bovine serum albumin as placebo (2 mg/kg), or with low (2 mg/kg) or high doses (20 mg/kg) of gelsolin. Samples were harvested at 8, 24, 48 and 72 hours postburn. The immune function of splenic T cells was analyzed. Cerebral pathology was examined by hematoxylin/eosin staining, while activated glial cells and infiltrating leukocytes were detected by immunohistochemistry. Cerebral cytokine mRNAs were further assessed by quantitative real-time PCR, while apoptosis was evaluated by caspase-3. Neural damage was determined using enzyme-linked immunosorbent assay of neuron-specific enolase (NSE) and soluble protein-100 (S-100). Finally, cerebral phospho-ERK expression was measured by western blot.

Results

Gelsolin significantly improved the outcomes of mice following major burns in a dose-dependent manner. The survival rate was improved by high dose gelsolin treatment compared with the placebo group (56.67% vs. 30%). Although there was no significant improvement in outcome in mice receiving low dose gelsolin (30%), survival time was prolonged against the placebo control (43.1 ± 4.5 h vs. 35.5 ± 5.0 h; P < 0.05). Burn-induced T cell suppression was greatly alleviated by high dose gelsolin treatment. Concurrently, cerebral abnormalities were greatly ameliorated as shown by reduced NSE and S-100 content of brain, decreased cytokine mRNA expressions, suppressed microglial activation, and enhanced infiltration of CD11b+ and CD45+ cells into the brain. Furthermore, the elevated caspase-3 activity seen following burn injury was remarkably reduced by high dose gelsolin treatment along with down-regulation of phospho-ERK expression.

Conclusion

Exogenous gelsolin infusion improves survival of mice following major burn injury by partially attenuating inflammation and apoptosis in brain, and by enhancing peripheral T lymphocyte function as well. These data suggest a novel and effective strategy to combat excessive neuroinflammation and to preserve cognition in the setting of major burns.
Xenotropic murine leukemia virus-related virus is not associated with chronic fatigue syndrome in patients from different areas of the us in the 1990s
Authors: Ali Mir A , Dale Janet K , Kozak Christine A , Goldbach-Mansky Raphaela , Miller Frederick W , Straus Stephen E , Cohen Jeffrey I
Published: September 2011

Background

In 2009, xenotropic murine leukemia virus-related virus (XMRV) was reported in 67% of patients with chronic fatigue syndrome (CFS) compared to 4% of controls. Since then numerous reports failed to detect XMRV in other cohorts of CFS patients, and some studies suggested that XMRV sequences in human samples might be due to contamination of these samples with mouse DNA.

Results

We determined the prevalence of XMRV in patients with CFS from similar areas in the United States as the original 2009 study, along with patients with chronic inflammatory disorders and healthy persons. Using quantitative PCR, we initially detected very low level signals for XMRV DNA in 15% of patients with CFS; however, the frequency of PCR positivity was no different between patients with CFS and controls. Repeated attempts to isolate PCR products from these reactions were unsuccessful. These findings were supported by our observations that PHA and IL-2 stimulation of peripheral blood mononuclear cells from patients with apparently low levels of XMRV, which induced virus replication in the 2009 report, resulted in the disappearance of the signal for XMRV DNA in the cells. Immunoprecipitation of XMRV-infected cell lysates using serum from patients from whom we initially detected low levels of XMRV DNA followed by immunoblotting with antibodies to XMRV gp70 protein failed to detect antibody in the patients, although one control had a weak level of reactivity. Diverse murine leukemia virus (MLV) sequences were obtained by nested PCR with a similar frequency in CFS patients and controls. Finally, we did not detect XMRV sequences in patients with several chronic inflammatory disorders including rheumatoid arthritis, Bechet's disease, and systemic lupus erythematosus.

Conclusions

We found no definitive evidence for XMRV DNA sequences or antibody in our cohort of CFS patients, which like the original 2009 study, included patients from diverse regions of the United States. In addition, XMRV was not detected in a cohort of patients with chronic inflammatory disorders.
Exercise prior to a freely requested meal modifies pre and postprandial glucose profile, substrate oxidation and sympathovagal balance
Authors: Charlot Keyne , Pichon Aurélien , Chapelot Didier
Published: September 2011

Background

The effects of exercise on glucose and metabolic events preceding and following a freely initiated meal have never been assessed. Moreover, the relationship between these events and sympathovagal balance is not known. The objective of this study was to determine whether exercise prior to a freely requested meal modifies the pre- and postprandial glucose profile, substrate oxidation and sympathovagal balance.

Methods

Nine young active male subjects consumed a standard breakfast (2298 ± 357 kJ). After 120 min, they either performed 75 min of exercise on a cycle ergometer (EX - 70% VO2max) or rested (RT). Lunch was freely requested but eatenad libitumonly during the 1stsession, and then energy intake was fixed across conditions. Glucose and sympathovagal balance were assessed continuously using a subcutaneous glucose monitoring system and analysis of heart rate variability, respectively. Every 5 min, a mean value was calculated for both glucose and sympathovagal balance. Substrate oxidation was determined by calculating the gas exchange ratio when lunch was requested and 180 min after the onset of eating.

Results

Preprandial glucose profiles were found in 72% of the sessions and with a similar frequency under both conditions. Meals were requested after a similar delay (40 ± 12 and 54 ± 10 min in EX and RT respectively; ns). At meal request, sympathovagal balance was not different between conditions but CHO oxidation was lower and fat oxidation higher in EX than in RT (-46% and +63%, respectively; both p < 0.05). Glucose responses to the meal were higher in incremental (+ 48%) but not in absolute value in EX than in RT, with a higher fat oxidation (+ 46%, p < 0.05), and a greater vagal withdrawal (+ 15%, p < 0.05).

Conclusions

These results show that exercise does not impair preprandial glucose declines at the following meal freely requested, but leads to an increased postprandial glucose response and an elevated fat oxidation, an effect that vagal withdrawal may contribute to explain.
Permanent Relief from Intermittent Cold Stress-Induced Fibromyalgia-Like Abnormal Pain by Repeated Intrathecal Administration of Antidepressants
Authors: Nishiyori Michiko , Uchida Hitoshi , Nagai Jun , Araki Kohei , Mukae Takehiro , Kishioka Shiroh , Ueda Hiroshi
Published: September 2011

Background:

Fibromyalgia (FM) is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS).

Results:

In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief.

Conclusions:

These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.
The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity
Authors: Rapicavoli Nicole A , Poth Erin M , Zhu Heng , Blackshaw Seth
Published: September 2011

Background

Thousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored.

Results

Here we characterize the expression and function of Six3OS, a long non-coding RNA that is transcribed from the distal promoter region of the gene encoding the homeodomain transcription factor Six3. Overexpression and knockdown analysis of Six3OS reveals that it plays an essential role in regulating retinal cell specification. We further observe that Six3OS regulates Six3 activity in developing retina, but does not do so by modulating Six3 expression. Finally, we show that Six3OS binds directly to Ezh2 and Eya family members, indicating that Six3OS can act as a molecular scaffold to recruit histone modification enzymes to Six3 target genes.

Conclusions

Our findings demonstrate a novel mechanism by which promoter-associated long non-coding RNAs can modulate the activity of their associated protein coding genes, and highlight the importance of this diverse class of molecules in the control of neural development.
Hyperferritinemia without iron overload in patients with bilateral cataracts: a case series
Authors: Kröger Arne , Bachli Esther B , Mumford Andrew , Gubler Christoph
Published: September 2011

Introduction

Hepatologists and internists often encounter patients with unexplained high serum ferritin concentration. After exclusion of hereditary hemochromatosis and hemosiderosis, rare disorders like hereditary hyperferritinemia cataract syndrome should be considered in the differential diagnosis. This autosomal dominant syndrome, that typically presents with juvenile bilateral cataracts, was first described in 1995 and has an increasing number of recognized molecular defects within a regulatory region of the L-ferritin gene (FTL).

Case presentation

Two patients (32 and 49-year-old Caucasian men) from our ambulatory clinic were suspected as having this syndrome and a genetic analysis was performed. In both patients, sequencing of the FTL 5' region showed previously described mutations within the iron responsive element (FTL c.33 C > A and FTL c.32G > C).

Conclusion

Hereditary hyperferritinemia cataract syndrome should be considered in all patients with unexplained hyperferritinemia without signs of iron overload, particularly those with juvenile bilateral cataracts. Liver biopsy and phlebotomy should be avoided in this disorder.
Molecular study of the perforin gene in familial hematological malignancies
Authors: El Abed Rim , Bourdon Violaine , Voskoboinik Ilia , Omri Halima , Youssef Yosra Ben , Laatiri Mohamed Adnene , Huiart Laetitia , Eisinger François , Rabayrol Laetitia , Frenay Marc , Gesta Paul , Demange Liliane , Dreyfus Hélène , Bonadona Valérie , Dugast Catherine , Zattara Hélène , Faivre Laurence , Zaier Monia , Jemni Saloua Yacoub , Noguchi Testsuro , Sobol Hagay , Soua Zohra
Published: September 2011

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in thePRF1coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutatedPRF1in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein.
Exome sequencing identifies a missense mutation in Isl1associated with low penetrance otitis media in dearisch mice
Authors: Hilton Jennifer M , Lewis Morag A , Grati M'hamed , Ingham Neil , Pearson Selina , Laskowski Roman A , Adams David J , Steel Karen P
Published: September 2011

Background

Inflammation of the middle ear (otitis media) is very common and can lead to serious complications if not resolved. Genetic studies suggest an inherited component, but few of the genes that contribute to this condition are known. Mouse mutants have contributed significantly to the identification of genes predisposing to otitis media

Results

The dearisch mouse mutant is an ENU-induced mutant detected by its impaired Preyer reflex (ear flick in response to sound). Auditory brainstem responses revealed raised thresholds from as early as three weeks old. Pedigree analysis suggested a dominant but partially penetrant mode of inheritance. The middle ear of dearisch mutants shows a thickened mucosa and cellular effusion suggesting chronic otitis media with effusion with superimposed acute infection. The inner ear, including the sensory hair cells, appears normal. Due to the low penetrance of the phenotype, normal backcross mapping of the mutation was not possible. Exome sequencing was therefore employed to identify a non-conservative tyrosine to cysteine (Y71C) missense mutation in the Islet1 gene, Isl1
Drsh
. Isl1 is expressed in the normal middle ear mucosa. The findings suggest the Isl1
Drsh
mutation is likely to predispose carriers to otitis media.

Conclusions

Dearisch, Isl1
Drsh
, represents the first point mutation in the mouse Isl1 gene and suggests a previously unrecognized role for this gene. It is also the first recorded exome sequencing of the C3HeB/FeJ background relevant to many ENU-induced mutants. Most importantly, the power of exome resequencing to identify ENU-induced mutations without a mapped gene locus is illustrated.
New method for the analysis of process rotating machine shop vibration test
Authors: Almasi A
Published: September 2011

Factory approval test (FAT) or shop run test is a unique opportunity to evaluate rotating machine performance before delivery to site. This note presents a new adaptive signal processing method to evaluate vibration measurement during FAT based on obtained noisy data. It is also a necessary step for machine reliability, fault diagnosis, future predictive maintenance, and condition monitoring.
Monte Carlo Algorithms for Default Timing Problems
Authors: Giesecke Kay , Kim Baeho , Zhu Shilin
Published: September 2011

Dynamic, intensity-based point process models are widely used to measure and price the correlated default risk in portfolios of credit-sensitive assets such as loans and corporate bonds. Monte Carlo simulation is an important tool for performing computations in these models. This paper develops, analyzes, and evaluates two simulation algorithms for intensity-based point process models. The algorithms extend the conventional thinning scheme to the case where the event intensity is unbounded, a feature common to many standard model formulations. Numerical results illustrate the performance of the algorithms for a familiar top-down model and a novel bottom-up model of correlated default risk.

This paper was accepted by Assaf Zeevi, stochastic models and simulation.
Optimal Compensation and Pay-Performance Sensitivity in a Continuous-Time Principal-Agent Model
Authors: Ju Nengjiu , Wan Xuhu
Published: September 2011

This paper studies the optimal contract between risk-neutral shareholders and a constant relative risk-aversion manager in a continuous-time model. Several interesting results are obtained. First, the optimal compensation is increasing but concave in output value if the manager is more risk averse than a log-utility manager. Second, when the manager has a log utility, a linear contract is optimal when there is no explicit lower bound on the compensation, and an option contract is optimal when there is an explicit lower bound. Third, optimal effort is stochastic (state dependent). Fourth, consistent with empirical findings and contrary to standard agency theory predictions, the relationship between pay-performance sensitivity and firm performance and that between pay-performance sensitivity and firm risk can be nonmonotonic.

This paper was accepted by Wei Xiong, finance.
A Combinatorial Proof of a Recursive Formula for Multipartitions
Authors: Lazarev Oleg , Swisher Holly
Published: September 2011

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Differentially Organized Top-Down Modulation of Prepulse Inhibition of Startle
Authors: Du Yi , Wu Xihong , Li Liang
Published: September 2011

Prepulse inhibition (PPI) of startle is the suppression of the startle reflex when a weaker sensory stimulus (the prepulse) shortly precedes the startling stimulus. PPI can be attentionally enhanced in both humans and laboratory animals. This study investigated whether the following three forebrain structures, which are critical for initial cortical processing of auditory signals, auditory fear conditioning/memories, and spatial attention, respectively, play a role in the top-down modulation of PPI in rats: the primary auditory cortex (A1), lateral nucleus of the amygdala (LA), and posterior parietal cortex (PPC). The results show that, under the noise-masking condition, PPI was enhanced by fear conditioning of the prepulse in a prepulse-specific manner, and the conditioning-induced PPI enhancement was further increased by perceptual separation between the conditioned prepulse and the noise masker. Reversibly blocking glutamate receptors in the A1 with 2 mmkynurenic acid eliminated both the conditioning-induced and perceptual separation-induced PPI enhancements. Blocking the LA eliminated the conditioning-induced but not the perceptual separation-induced PPI enhancement, and blocking the PPC specifically eliminated the perceptual separation-induced PPI enhancement. The two types of PPI enhancements were also eliminated by the extinction manipulation. Thus, the top-down modulation of PPI is differentially organized and depends on operations of various forebrain structures. Due to the fine-tuned modulation by higher-order cognitive processes, functions of PPI can be more flexible to complex environments. The top-down enhancements of PPI in rats are also useful for modeling some mental disorders, such as schizophrenia, attention deficit/hyperactivity disorder, and posttraumatic stress disorder.
Opioidergic Interactions between Striatal Projection Neurons
Authors: Blomeley Craig P. , Bracci Enrico
Published: September 2011

Medium spiny striatal projection neurons (MSNs) release opioid neuropeptides, but the role of these neurotransmitters is still poorly understood. While presynaptic inhibition of corticostriatal axons by opioid receptors has been demonstrated using exogenous ligands, the action of synaptically released opioids in the striatum has not been investigated. We performed single and paired whole-cell recordings from rat MSNs while corticostriatal fibers were electrically activated. In single recording experiments, we also activated antidromically the axons of a population of MSNs. Corticostriatal fibers were stimulated once every 10 s and every other stimulation was preceded by 5 antidromic spikes (at 100 Hz). This burst of antidromic spikes produced robust inhibition of evoked corticostriatal responses. This inhibition was not affected by the δ-opioid receptor antagonist SDM25N, but was completely abolished by the μ-opioid receptor antagonist CTOP. Inhibitory effects were maximal (on average 29.6 ± 11.4%) when the burst preceded the corticostriatal stimulation by 500 ms and became undetectable for intervals >2 s. Paired recordings from MSNs located <100 μm apart revealed that, in 30 of 56 (54%) pairs, a burst of five action potentials in one of the MSNs caused significant inhibition (17.1 ± 5.7%) of evoked glutamatergic responses in the other MSN. In 5 of these pairs, reciprocal inhibition of corticostriatal inputs was present. These effects were maximal 500 ms after the burst and were completely blocked by CTOP. Thus, these results reveal a novel, strong opioid-mediated communication between MSNs and provide a new cellular substrate for competitive dynamics in the striatum.
Glutamate Spillover between Mammalian Cone Photoreceptors
Authors: Szmajda Brett A. , DeVries Steven H.
Published: September 2011

Cone photoreceptors transmit signals at high temporal frequencies and mediate fine spatial vision. High-frequency transmission requires a high rate of glutamate release, which could promote spillover to neighboring cells, whereas spatial vision requires that cones within a tightly packed array signal light to postsynaptic bipolar cells with minimal crosstalk. Glutamate spread from the cone terminal is thought to be limited by presynaptic transporters and nearby glial processes. In addition, there is no ultrastructural evidence for chemical synapses between mammalian cones, although such synapses have been described in lower vertebrate retinas. We tested for cone–cone glutamate diffusion by recording from adjacent cone pairs in the ground squirrel retina, and instead found that the glutamate released by one cone during electrical stimulation activates glutamate transporter Cl−conductances on neighboring cones. Unlike in other systems, where crosstalk is diminished by increasing the temperature and by moving to a more intact preparation, glutamate spread persisted at physiological temperatures (37°C) and in retinal flat mounts. The glutamate-gated anion conductance in cones has a reversal potential of ∼−30 mV compared with a cone resting potential of ∼−50 mV; thus, crosstalk should have a depolarizing effect on the cone network. Cone–cone glutamate spread is regulated by the physiological stimulus, light, and under physiological conditions can produce a response of ∼2 mV, equivalent to 13–20% of a cone's light response. We conclude that in the absence of discrete chemical synapses, glutamate flows between cones during a light response and may mediate a spatially distributed positive feedback.
Behavioral Evidence for a Glucose Polymer Taste Receptor That Is Independent of the T1R2+3 Heterodimer in a Mouse Model
Authors: Treesukosol Yada , Smith Kimberly R. , Spector Alan C.
Published: September 2011

Although it is clear that the heterodimer formed by the T1R2 and T1R3 proteins serves as the primary taste receptor for sweeteners, there is growing evidence that responses to glucose polymers may be mediated by a different taste receptor. Here we report that although T1R2 knock-out (KO) and T1R3 KO mice displayed severely impaired responding to glucose, maltose, and maltotriose in an initial session of a brief-access taste test (5 s trials, 25 min sessions) relative to wild-type (WT) mice, they subsequently increased their licking as a function of concentration for maltose and maltotriose with continued testing, presumably due to associating weak oral cues with positive post-ingestive consequences. Interestingly, these KO mice displayed relatively normal concentration-dependent licking to Polycose, a mixture of glucose polymers, even in the first session. Importantly, the experience-dependent increase in responsiveness to the sugars observed with the T1R2 and T1R3 single KO mice was not statistically significant in the T1R2/3 double KO mice. The double KO mice, however, still displayed significant concentration-dependent responding to Polycose in the first test session, albeit lick rates were slightly lower than those seen for WT mice, perhaps because small amounts of glucose, maltose, and maltotriose found in Polycose were enhancing the signal in WT mice or because T1R2 or T1R3 can possibly heteromerize with another protein to form a fully functional glucose polymer receptor. These findings provide behavioral evidence that glucose polymers, with an optimal chain length greater than three glucose moieties, stimulate a taste receptor independent of the T1R2+3 heterodimer.