bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Characteristics of Blood Pressure Profiles and Stroke Outcomes in the ECASS-II Trial
Authors: Yong Mei , Kaste Markku
Published: December 2007

Background and Purpose—

Certain characteristics of early blood pressure (BP) profiles were reported to be independent predictors of long-term outcome in the first European Cooperative Acute Stroke Study (ECASS-I) trial. The aim of the study was to find out the association of BP profiles with functional outcome, mortality, and hemorrhagic complications in the ECASS-II database.

Methods—

We studied 793 patients with acute ischemic hemispheric stroke in the ECASS-II. After randomization, BP was measured every 15 minutes during the first 2 hours, then every 30 minutes during the first 8 hours, and thereafter at 1-hour intervals up to 24 hours. Individual 0- to 24-hour BP profiles were characterized by baseline, maximum, minimum, and mean BP and successive variation of the profile. The end points were favorable outcome (modified Rankin Scale score of 0 or 1) at day 90, all-cause mortality at day 90, and hemorrhagic transformation within the first 7 days.

Results—

High baseline, maximum, mean level, and variability of systolic BP profiles were each inversely associated with favorable outcome (OR=0.84, 95% CI: 0.74 to 0.94; OR=0.82, 95% CI: 0.73 to 0.91; OR=0.81, 95% CI: 0.71 to 0.93; OR=0.57, 95% CI: 0.35 to 0.92, respectively) and associated with an increased risk of parenchymal hemorrhage within the first 7 days (OR=1.27, 95% CI: 1.07 to 1.51; OR=1.49, 95% CI: 1.27 to 1.75; OR=1.52, 95% CI: 1.23 to 1.87; OR=2.62, 95% CI: 1.40 to 4.87; respectively) in recombinant tissue plasminogen activator-treated patients. In placebo-treated patients, high maximum, mean level, and successive variation of systolic BP profiles were inversely associated with favorable outcome (OR=0.76, 95% CI: 0.66 to 0.86; OR=0.76, 95% CI: 0.65 to 0.89; OR=0.41, 95% CI: 0.22 to 0.76; respectively), although the association of baseline systolic BP and favorable outcome was not significant (OR=0.91, 95% CI: 0.80 to 1.03). No association with hemorrhagic transformation was found, even after the adjustment.

Conclusions—

The hemorrhagic transformation within the first 7 days and favorable outcome were independently associated with dynamics of BP within the first 24 hours after an acute ischemic stroke in patients treated with thrombolysis, but in placebo-treated patients, only with favorable outcome. Continuous BP monitoring is hence important for the prognosis and gives implications to optimize BP management, particularly regarding a reasonable BP level and stability.
Treatment of Hyperglycemia In Ischemic Stroke (THIS)
Authors: Bruno Askiel , Kent Thomas A. , Coull Bruce M. , Shankar Ravi R. , Saha Chandan , Becker Kyra J. , Kissela Brett M. , Williams Linda S.
Published: December 2007

Background and Purpose—

Hyperglycemia may worsen brain injury during acute cerebral infarction. We tested the feasibility and tolerability of aggressive hyperglycemia correction with intravenous insulin compared with usual care during acute cerebral infarction.

Methods—

We conducted a randomized, multicenter, blinded pilot trial for patients with cerebral infarction within 12 hours after onset, a baseline glucose value ≥8.3 mmol/L (≥150 mg/dL), and a National Institutes of Health Stroke Scale score of 3 to 22. Patients were randomized 2:1 to aggressive treatment with continuous intravenous insulin or subcutaneous insulin QID as needed (usual care). Target glucose levels were <7.2 mmol/L (<130 mg/dL) in the aggressive-treatment group and <11.1 mmol/L (<200 mg/dL) in the usual-care group. Glucose was monitored every 1 to 2 hours, and the protocol treatments continued for up to 72 hours. Final clinical outcomes were assessed at 3 months.

Results—

We randomized 46 patients (31 to aggressive treatment and 15 to usual care). All patients in the aggressive-treatment group and 11 (73%) in the usual-care group had diabetes (
P
=0.008). Glucose levels were significantly lower in the aggressive-treatment group throughout protocol treatment (7.4 vs 10.5 mmol/L [133 vs 190 mg/dL],
P
<0.001). Hypoglycemia <3.3 mmol/L (<60 mg/dL) occurred only in the aggressive-treatment group (11 patients, 35%), 4 (13%) of whom had brief symptoms, including only 1 (3%) neurologic. Final clinical outcomes were nonsignificantly better in the aggressive-treatment group.

Conclusions—

The intravenous insulin protocol corrected hyperglycemia during acute cerebral infarction significantly better than usual care without major adverse events and should be investigated in a clinical efficacy trial.
To Invest or Insure?
Authors: Wright Joseph
Published: December 2007

In this article, the author argues that the time horizon a dictator faces affects his incentives over the use of aid in three ways. First, dictators have a greater incentive to invest in public goods when they have a long time horizon. Second, dictators with short time horizons often face the threat of challengers to the regime; this leads them to forgo investment and instead consume state resources in two forms that harm growth: repression and private pay-offs to political opponents. Third, dictators with short time horizons have a strong incentive to secure personal wealth as a form of insurance in case the regime falls. Using panel data on dictatorships in 71 developing countries from 1961 to 2001, the author finds that time horizons have a positive impact on aid effectiveness: Foreign aid is associated with positive growth when dictators face long time horizons and negative growth when time horizons are short.
Moralistic Street Robbery
Authors: Jacobs Bruce A. , Wright Richard
Published: December 2007

Street robbery is widely seen as the epitome of acquisitive instrumentality, yet recent research suggests that the crime may be designed more to send a message than to generate capital. Drawing from in-depth, semistructured interviews with active offenders, we find that moralistic street robbery is a response to one of three types of violations. Market-related violations emerge from disputes involving partners in trade, rivals, or generalized predators. Status-based violations involve encounters in which the grievant's essential character or normative sensibilities have been challenged. Personalistic violations flow from incidents in which the grievant's autonomy or belief in a just world have been jeopardized. Discussion focuses on the data's implications for deterrence and the spread of urban violence.
Psychometric Properties of the Beck Depression Inventory—II (BDI-II) Among Community-Dwelling Older Adults
Authors: Segal Daniel L. , Coolidge Frederick L. , Cahill Brian S. , O'Riley Alisa A.
Published: December 2007

The psychometric properties of the Beck Depression Inventory—II (BDI-II) as a self-administered screening tool for depressive symptoms were examined in a sample of community-dwelling older and younger adults. Participants completed the BDI-II, the Center for Epidemiologic Studies Depression Scale, the Coolidge Axis II Inventory, the Perceived Stress Scale, and the Short Psychological Well-Being Scale. Internal reliability of the BDI-II was found to be good among older and younger adults. The average BDI-II depression score did not differ between younger and older adults. Solid evidence for convergent and discriminant validity was demonstrated by correlations between the BDI-II with the other measures. The BDI-II appears to have strong psychometric support as a screening measure for depression among older adults in the general population. Implications for using the BDI-II as an assessment instrument in behaviorally based psychotherapy are discussed.
A Review of Behavioral Treatments for Self-Injurious Behaviors of Persons With Autism Spectrum Disorders
Authors: Matson Johnny L. , LoVullo Santino V.
Published: December 2007

Autism spectrum disorders (ASD) are considered to be among the most serious of the mental health conditions. Concomitant with many cases of ASD is intellectual disability. Further compounding the disability is the fact that both conditions are known risk factors for self-injurious behavior (SIB). To date, the most effective intervention methods, based on the available data, appear to be variants of behavior modification. This article provides an overview of the current status of learning-based interventions for SIB in ASD and provides a review of specific studies. Although most studies describe some combination of reinforcement and punishment procedures, efforts are under way to develop more positively oriented strategies, such as functional assessment, to decrease the use of punishment. However, almost all the treatment studies employ single case designs, thus preventing a comparison of treatment efficacy. These issues are discussed along with other strengths, weaknesses, and future directions for clinical practice and treatment.
The Law Enforcement Officer Stress Survey (LEOSS)
Authors: Van Hasselt Vincent B. , Sheehan Donald C. , Malcolm Abigail S. , Sellers Alfred H. , Baker Monty T. , Couwels Judy
Published: December 2007

This study establishes the reliability and validity of the Law Enforcement Officer Stress Survey (LEOSS), a short early-warning stress-screening measure for law enforcement officers. The initial phase of LEOSS development employed the behavioral-analytic model to construct a 25-item instrument specifically geared toward evaluation of stress in this population. The purpose of the present study was to examine psychometric properties of the LEOSS. Results indicate this instrument has good levels of internal consistency, testretest reliability, and validity. Potential applications of the LEOSS in clinical and research contexts are discussed. The next phase of research on the LEOSS is discussed, and suggestions for directions that future research in this area might take are offered.
Technology Movements and the Politics of Free/Open Source Software
Authors: McInerney Paul-Brian
Published: December 2007

Many technologies in our everyday lives are expressions of deliberate and protracted political struggles among interested groups. While some technologies are inherently political, other technologies become politicized through competition among different groups and organizations. How do seemingly apolitical technologies become politicized? In this article, the author examines the case of the “circuit riders,” a progressive technology movement in the United States that promotes information technology use among nonprofit and grassroots organizations, to show how a particular technology is politicized through field-level interactions. Applying and contributing to actor—network theory, the author finds that translation takes place as an organizational process by which actors associate the ideals of the technology in question with their political ideals and then attempt to enroll other actors to accept the resultant associations. Successful association depends on both discursive and organizational practices.
The Contributions of Race, Individual Socioeconomic Status, and Neighborhood Socioeconomic Context on the Self-Rated Health Trajectories and Mortality of Older Adults
Authors: Li Yao  , Robert Stephanie A.
Published: December 2007

Drawing on four waves of the Americans' Changing Lives Study, we examine the contributions of individual and neighborhood socioeconomic status to explain racial disparities in self-rated health trajectories over time, among Black and White older adults in the United States. Primary results of three-level growth curve analyses of self-rated health change, and multinomial logistic regression of mortality and attrition, indicate that (1) racial and socioeconomic disparities in health persist into old age, (2) Black older adults have greater declines in self-rated health over time than White older adults, and these disparities are explained by individual and neighborhood socioeconomic status (SES), (3) individual and neighborhood SES contribute to persisting self-rated health disparities at older ages, but may not contribute significantly to further declines in self-rated health at older ages, (4) Black disadvantage in mortality exists at older ages, and persists net of individual and neighborhood SES, and (5) individual SES is a significant predictor of 16-year mortality among older adults. Our results suggest that we should continue to be concerned about the existence and persistence of racial and socioeconomic disparities in self-rated health and mortality throughout old age, and the contribution of individual and neighborhood socioeconomic context in perpetuating these disparities.
Characterization of Structurally Related Adenovirus-laden Silk-elastinlike Hydrogels
Authors: Dandu Ramesh , Ghandehari Hamidreza , Cappello Joseph
Published: December 2007

Genetically engineered silk-elastinlike protein polymer (SELP) analogs, SELP-47 K and -415 K, consisting of varying ratio(s) and length(s) of silk and elastin in their monomer repeats and capable of spontaneous hydrogel formation were evaluated as matrices for controlled adenoviral release in vitro. The degree of swelling (q) and the amount of soluble fraction of SELP hydrogel analogs were evaluated with and without the incorporation of adenoviruses. The results indicate that polymer concentration and structure and not the incorporated adenoviruses are the predominant factors that influence q and the soluble fraction in these hydrogels over a 28-day period. The release of adenoviruses was a function of polymer concentration and structure. The higher cumulative percentage release observed in SELP-415 K compared to SELP-47 K can be attributed to the longer elastin sequence in the polymer backbone. These results indicate the potential of customizing the network properties and release from SELPs by manipulating the macromolecular architecture using recombinant synthesis.
Synthesis and In vivo Studies of Protein C-loaded Nanoparticles with PEO Modified Surfaces
Authors: Chognot David , Six Jean-Luc , Léonard Michèle , Dellacherie Edith , Faivre Béatrice , Bonneaux François , Vigneron Claude
Published: December 2007

Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared by double emulsion/solvent evaporation using water-soluble biocompatible copolymers of MPEO and polylactide, as surfactants of the secondary emulsion. The nanoparticle preparation was optimized to obtain the best yield of encapsulated protein C and provide the greatest retention of its biological activity. The nanoparticles were characterized in terms of size, zeta potential, and thickness of the MPEO external layer. Protein C-loaded nanoparticles were injected into the bloodstream of guinea pigs and the protein concentration in plasma is measured as a function of time. After a rapid release corresponding to 20% of the injected protein, the protein plasma concentration progressively decreased and reached a value close to zero after 5 h. Consequently, the in vivo fate of the fluorescent nanoparticles coated with or without MPEO is studied. The uncoated nanoparticles were rapidly captured by the circulating granulocytes while the coated ones were not. The histological analysis of the spleen, 1 hour after injection, showed that the MPEO-coated particles were retained in this organ, while the uncoated ones were not captured.
Some Experimental and Theoretical Investigations on Fire Retardant Coir/Epoxy Micro-Composites
Authors: Misra R.K. , Kumar Sandeep , Sandeep K. , Misra Ashok
Published: December 2007

This article reports some experimental and theoretical investigations on fire retardant coir/epoxy micro-composites. The coir fiber is treated with saturated bromine water for increasing the electrical properties and then mixed with stannous chloride solution for improving the fire retardant properties. Only 5% (approximately) of fire retardant filler reduces the smoke density by 25% and the LOI value increases to 24%. The mechanical properties of the coir/epoxy micro-composites are not affected much after incorporation of filler. Flexural strength and flexural modulus of the NET increases tremendously compared to NEU and NE. Multiquadric radial basis function (MQRBF) method is applied for static and dynamic analysis of coir/epoxy micro-composite plate under uniformly distributed load. Damping behavior and natural frequencies are observed in NE, NEU, and NET. MQRBF is applied for spatial discretization and Newmark implicit scheme is used for temporal discretization. The discretization of the differential equations generates greater number of algebraic equations than the unknown coefficients. The multiple linear regression analysis, which is based on the least square error norm, is employed to obtain the coefficients. Simple supported and clamped boundary conditions are considered for verification of present results and they are compared with other existing analytical methods.
Expanding Nursing Perspectives on Loss and Grieving
Authors: Beryl Pilkington F.
Published: December 2007

This column seeks to contribute to the understanding of the concept of grieving a loss through capturing the indivisible, unpredictable, everchanging nature of this universal human experience. Through the process of concept inventing the extant theoretical knowledge concerning grief and loss, classical literature, and the humanbecoming theory and research literature were considered, revealing the idea that grieving a loss is persistent but the meaning of the experience continually changes. Knowledge of the persistent, everchanging nature of grieving a loss is important for nurses who use humanbecoming theory as a guide while abiding with those who grieve a loss.
The Gifts of Silence and Solitude
Authors: Schmidt Bunkers Sandra
Published: December 2007

In this column the author describes the importance of finding silence and solitude amid the noise and technology present today in the teaching-learning academy. Three gifts of silence and solitude are identified: the gift of comforting aloneness, the gift of vision for new horizons, and the gift of a sense of freedom. A humanbecoming perspective is used to explore the implications of these gifts. This column introduces a column by Diana Vander Woude describing her teaching-learning experience in leadership focusing on silence and solitude.
Is Hope Fragile?
Authors: Baumann Steven L.
Published: December 2007

The communication of bad news to patients in a sensitive and supportive manner is a challenging part of healthcare practice, in part because of the cultural differences and ethical dilemmas that complicate such discussions. One of the barriers to nurse-patient communication has been the assumption that hope is fragile. Sometimes this assumption is held by nurses, and sometimes it is held by patients or their families. Reasons for confidence in hope are discussed.
Bodycote Prize 2006: Best Technical/Scientific Paper Novel ceramic Ti–Si–C nanocomposite coatings for electrical contact applications
Authors: Eklund P.
Published: December 2007

Nanocomposite coatings consisting of TiC nanocrystallites embedded in an amorphous SiC matrix (nc-TiC/a-SiC) have been produced using magnetron sputtering from a Ti3SiC2 target onto electrical contact components at a temperature below 300°C. The as deposited nanocomposites were employed as electrical contact materials. Results show that when contacted against Ag, they exhibit somewhat higher contact resistance than Ag against Ag, while preventing welding and potentially minimising wear. This is due to an adequate resistivity coupled with beneficial mechanical properties. The design of the nanoscale materials produced coatings with a relatively high nanoindentation hardness of 20 GPa, but with a ductile deformation behaviour. The ductility is explained by rotation and gliding of nc-TiC grains in the matrix. Therefore, the nanocomposite material can minimise problems with wear and welding while retaining low contact resistance. Consequently, this type of novel coating with appropriate mechanical properties offers a solution to problems in many electrical applications. Moreover, the use of physically vapour deposited coatings is promoted in some previously relatively unexploited areas of electrical contact applications.
Electrodeposition of platinum metal on titanium and anodised titanium from P salt: Application to electro-oxidation of glycerol
Authors: Hosseini M. G. , Sajjadi S. A. S. , Momeni M. M.
Published: December 2007

Pt/Ti and Pt/TiO2 electrodes were made by galvanic deposition of platinum metal from an acid plating bath containing cis-dinitro-diammin-platinum(II) complex (P salt) onto titanium and anodic TiO2 layer on titanium substrates respectively. Titanium oxide nanotubes were fabricated by anodising titanium foil in acid solution. Pt/Ti and Pt/TiO2 electrodes were characterised using electrochemical methods and scanning electron microscopy. Cyclic voltammetric analysis of Pt/Ti electrodes in dilute sulphuric acid yields voltammograms with features characteristic of bulk polycrystalline platinum electrodes. In contrast, the voltammograms for Pt/TiO2 electrodes are not quantitatively similar to those for smooth polycrystalline platinum electrodes. Voltammetry in potassium ferricyanide yields reversible voltammograms, indicating the good electrical conductivity of and connectivity between the deposited platinum and substrates and hence the absence of any significant resistive surface oxide film. The electrocatalytic behaviour of this type of electrodes in the glycerol electro-oxidation was studied.
Influence of shot peening on fatigue property of Ti-60 high temperature titanium alloy
Authors: Gao Y. K.
Published: December 2007

The changes of surface topography, surface roughness, surface residual stress and compressive residual stress field caused by shot peening and their effects on fatigue properties of Ti-60 high temperature titanium alloy at 20 and 600°C were investigated. The results show that the fatigue limit for 1 × 107 cycles is increased by ∼39 and 15% by shot peening at 20 and 600°C respectively.
Glucose-6-phosphate dehydrogenase deficiency: a historical perspective
Authors: Beutler Ernest
Published: December 2007

Glucose-6-phosphate dehydrogenase deficiency serves as a prototype of the many human enzyme deficiencies that are now known. Since its discovery more than 50 years ago, the high prevalence of the defect and the easy accessibility of the cells that manifest it have made it a favorite tool of biochemists, epidemiologists, geneticists, and molecular biologists as well as clinicians. In this brief historical review, we trace the discovery of this defect, its clinical manifestations, detection, population genetics, and molecular biology.
Galactosylation does not prevent the rapid clearance of long-term, 4°C-stored platelets
Authors: Wandall Hans H. , Hoffmeister Karin M. , Sørensen Anne Louise , Rumjantseva Viktoria , Clausen Henrik , Hartwig John H. , Slichter Sherrill J.
Published: December 2007

Cold storage of platelets for transfusion is desirable to extend platelet storage times and to prevent bacterial growth. However, the rapid clearance of cold-stored platelets prevents their use. A novel method for preventing the rapid clearance of cold-stored platelets has previously been developed in a murine model. Cold storage induces the clustering and recognition of exposed β-N-acetylglucosamine (βGlcNAc) on platelet surfaces. Glycosylation of βGlcNAc residues with uridine 5′-diphosphogalactose (UDP-galactose) results in the normal survival of short-term (2 h) 0°C-stored murine platelets. Based on this finding, we developed a similar glycosylation process by adding UDP-galactose to human apheresis platelets. A phase 1 clinical trial was conducted transfusing radiolabeled autologous apheresis platelets stored for 48 hours at 4°C with or without pretreatment with UDP-galactose. In contrast to the murine study, galactosylation of human platelets did not prevent the accelerated platelet clearance routinely observed after 4°C storage. We next developed a murine model of platelet storage for 48 hours at 4°C and showed that UDP-galactose treatment of murine platelets also did not prevent their rapid clearance, in agreement with the human platelet study. We conclude that different mechanisms of clearance may exist for short- and long-term cold-stored platelets.
DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL
Authors: Dulucq Stéphanie , St-Onge Geneviève , Gagné Vincent , Ansari Marc , Sinnett Daniel , Labuda Damian , Moghrabi Albert , Krajinovic Maja
Published: December 2007

Dihydrofolate reductase (DHFR) is the major target of methotrexate (MTX), a key component in childhood acute lymphoblastic leukemia (ALL) treatment. A total of 15 polymorphisms in DHFR promoter were analyzed, and 3 sites (C−1610G/T, C−680A, and A−317G) were identified as sufficient to define observed haplotypes (tag single nucleotide polymorphisms [tagSNPs]). These polymorphisms were investigated for association with treatment response in 277 children with ALL. Lower event-free survival (EFS) was associated with homozygosity for the allele A−317 and C−1610 (P = .03 and .02), and with the haplotype *1, defined by both C−1610 and A−317 alleles (P = .03). The haplotype *1 conferred higher transcriptional activity (P < .01 compared with haplotypes generating minimal luciferase expression). Quantitative mRNA analysis showed higher DHFR levels for particular haplotype *1 carriers (P < .01). The analysis combining haplotype *1 with thymidylate synthase (TS) and cyclin D1 (CCND1) genotypes previously shown to affect ALL outcome showed that the number of event-predisposing genotypes was associated with increasingly lower EFS (P < .001). In conclusion, DHFR promoter polymorphisms are associated with worse ALL outcome, likely due to a higher DHFR expression. Combined effects among genes of the folate cycle can further accentuate differences in the response to the treatment.
Braking platelet activation: deactivating the receptors
Authors: Rao Koneti A.
Published: December 2007

Glycoprotein (GP) VI and Fc receptor FcγRIIa are 2 ITAM (immunoreceptor tyrosine-activation motif)–bearing platelet surface receptors. In this issue of Blood, Gardiner and colleagues show that activation of either receptor results in simultaneous proteolytic cleavage of GPVI ectodomain and FcγRIIa cytoplasmic tail, providing distinct mechanisms for their down-regulation on platelet activation.
Ongoing improvement in long-term survival of patients with Hodgkin disease at all ages and recent catch-up of older patients
Authors: Brenner Hermann , Gondos Adam , Pulte Dianne
Published: December 2007

Since the breakthroughs in combination chemotherapy of patients with Hodgkin disease (HD) starting in the 1960s, prognosis of patients has been rising steadily. Trends in long-term survival of patients with HD on the population level should therefore be monitored in an as timely as possible manner. We assessed trends in age specific 5- and 10-year relative survival of patients with HD in the United States from 1980-1984 to 2000-2004 from the 1973-2004 database of the Surveillance, Epidemiology, and End Results (SEER) Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5-year relative survival steadily increased from 73.5% to 85.2% (+11.7 percentage units), and 10-year relative survival increased from 62.1% to 80.1% (+18.0 percentage units) between 1980-1984 and 2000-2004, according to period analysis. The increase was particularly pronounced for patients aged 45 to 59 years and 60 years and older (increases in 10-year relative survival by 24.8 and 23.3 percentage points, respectively). Nevertheless, a strong age gradient persisted, with 10-year relative survival of 92.7%, 88.7%, 84.9%, 76.2%, and 44.9% in patients aged 15 to 24 years, 25 to 34 years, 35 to 44 years, 45 to 54 years, and 60 years and older, respectively, in 2000-2004. Our period analysis discloses ongoing, major improvement in long-term survival of patients with HD in recent years, particularly among older patients.
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
Authors: Minamishima Yoji Andrew , Moslehi Javid , Bardeesy Nabeel , Cullen Darragh , Bronson Roderick T. , Kaelin William G.
Published: December 2007

Pharmacologic activation of the heterodimeric HIF transcription factor appears promising as a strategy to treat diseases, such as anemia, myocardial infarction, and stroke, in which tissue hypoxia is a prominent feature. HIF accumulation is normally linked to oxygen availability because an oxygen-dependent posttranslational modification (prolyl hydroxylation) marks the HIFα subunit for polyubiquitination and destruction. Three enzymes (PHD1, PHD2, and PHD3) capable of catalyzing this reaction have been identified, although PHD2 (also called Egln1) appears to be the primary HIF prolyl hydroxylase in cell culture experiments. We found that conditional inactivation of PHD2 in mice is sufficient to activate a subset of HIF target genes, including erythropoietin, leading to striking increases in red blood cell production. Mice lacking PHD2 exhibit premature mortality associated with marked venous congestion and dilated cardiomyopathy. The latter is likely the result of hyperviscosity syndrome and volume overload, although a direct effect of chronic, high-level HIF stimulation on cardiac myocytes cannot be excluded.
Lysosomal trafficking functions of mucolipin-1 in murine macrophages
Authors: Thompson Eric G , Schaheen Lara , Dang Hope , Fares Hanna
Published: December 2007

Background

Mucolipidosis Type IV is currently characterized as a lysosomal storage disorder with defects that include corneal clouding, achlorhydria and psychomotor retardation.MCOLN1, the gene responsible for this disease, encodes the protein mucolipin-1 that belongs to the "Transient Receptor Potential" family of proteins and has been shown to function as a non-selective cation channel whose activity is modulated by pH. Two cell biological defects that have been described in MLIV fibroblasts are a hyperacidification of lysosomes and a delay in the exit of lipids from lysosomes.

Results

We show that mucolipin-1 localizes to lysosomal compartments in RAW264.7 mouse macrophages that show subcompartmental accumulations of endocytosed molecules. Using stable RNAi clones, we show that mucolipin-1 is required for the exit of lipids from these compartments, for the transport of endocytosed molecules to terminal lysosomes, and for the transport of the Major Histocompatibility Complex II to the plasma membrane.

Conclusion

Mucolipin-1 functions in the efficient exit of molecules, destined for various cellular organelles, from lysosomal compartments.
MRPS18CP2 alleles and DEFA3absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene
Authors: Ballana Ester , Mercader Josep Maria , Fischel-Ghodsian Nathan , Estivill Xavier
Published: December 2007

Background

Mitochondrial DNA (mtDNA) mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified.

Methods

With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (DEFA3 gene absence, CLDN23 gene and MRPS18CP2 pseudogene) in a group of 213 A1555G carriers.

Results

Family based association studies identified a positive association for a polymorphism on MRPS18CP2 and an overrepresentation of DEFA3 gene absence in the deaf group of A1555G carriers.

Conclusion

Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation.
Immune system responses and fitness costs associated with consumption of bacteria in larvae of Trichoplusia ni
Authors: Freitak Dalial , Wheat Christopher W , Heckel David G , Vogel Heiko
Published: December 2007

Background

Insects helped pioneer, and persist as model organisms for, the study of specific aspects of immunity. Although they lack an adaptive immune system, insects possess an innate immune system that recognizes and destroys intruding microorganisms. Its operation under natural conditions has not been well studied, as most studies have introduced microbes to laboratory-reared insects via artificial mechanical wounding. One of the most common routes of natural exposure and infection, however, is via food; thus, the role of dietary microbial communities in herbivorous insect immune system evolution invites study. Here, we examine the immune system response and consequences of exposing a lepidopteran agricultural pest to non-infectious microorganisms via simple oral consumption.

Results

Immune system response was compared between Trichoplusia ni larvae reared on diets with or without non-pathogenic bacteria (Escherichia coli and Micrococcus luteus). Two major immune response-related enzymatic activities responded to diets differently – phenoloxidase activity was inhibited in the bacteria-fed larvae, whereas general antibacterial activity was enhanced. Eight proteins were highly expressed in the hemolymph of the bacteria fed larvae, among them immune response related proteins arylphorin, apolipophorin III and gloverin. Expression response among 25 putative immune response-related genes were assayed via RT-qPCR. Seven showed more than fivefold up regulation in the presence of bacterial diet, with 22 in total being differentially expressed, among them apolipophorin III, cecropin, gallerimycin, gloverin, lysozyme, and phenoloxidase inhibiting enzyme. Finally, potential life-history trade-offs were studied, with pupation time and pupal mass being negatively affected in bacteria fed larvae.

Conclusion

The presence of bacteria in food, even if non-pathogenic, can trigger an immune response cascade with life history tradeoffs. Trichoplusia ni larvae are able to detect and respond to environmental microbes encountered in the diet, possibly even using midgut epithelial tissue as a sensing organ. Potential benefits of this immune system priming may outweigh the observed tradeoffs, as priming based on environmentally sensed bacterial may decrease risk of serious infection. These results show that food plant microbial communities represent a dynamic and unstudied part of the coevolutionary interactions between plants and their insect herbivores.
Cyclooxygenase inhibition lowers prostaglandin E2 release from articular cartilage and reduces apoptosis but not proteoglycan degradation following an impact load in vitro
Authors: Jeffrey Janet E , Aspden Richard M
Published: December 2007

This study investigated the release of prostaglandin E2 (PGE2) from cartilage following an impact load in vitro and the possible chondroprotective effect of cyclooxygenase-2 (COX-2) inhibition using non-steroidal anti-inflammatory drugs (NSAIDs).

Explants of human articular cartilage were subjected to a single impact load in a drop tower, and then cultured for 6 days in the presence of either a selective COX-2 inhibitor (celecoxib; 0.01, 0.1, 1.0 and 10 μM) or a non-selective COX inhibitor (indomethacin; 0.1 and 10 μM). The concentrations of PGE2 and glycosaminoglycans (GAGs), a measure of cartilage breakdown, were measured in the explant culture medium at 3 and 6 days post-impact. Apoptotic cell death was measured in frozen explant sections by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method.

PGE2 levels were increased by more than 20-fold in the medium of explants at both 3 (p = 0.012) and 6 days (p = 0.004) following impact, compared with unloaded controls. In the presence of celecoxib and indomethacin, the PGE2 levels were reduced in a dose-related manner. These inhibitors, however, had no effect in reducing the impact-induced release of GAGs from the cartilage matrix. Addition of celecoxib and indomethacin significantly reduced the number of trauma-induced apoptotic chondrocytes in cartilage explant sections.

In this study, a marked increase in PGE2 was measured in the medium following an impact load on articular cartilage, which was abolished by the selective COX-2 inhibitor, celecoxib, and non-selective indomethacin. These inhibitors reduced chondrocyte apoptosis but no change was observed in the release of GAGs from the explants, suggesting that the COX/PGE2 pathway is not directly responsible for cartilage breakdown following traumatic injury. Our in vitro study demonstrates that it is unlikely that COX-2 inhibition alone would slow down or prevent the development of secondary osteoarthritis.
The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients
Authors: Nguyen Nam Q , Fraser Robert J , Bryant Laura K , Chapman Marianne J , Wishart Judith , Holloway Richard H , Butler Ross , Horowitz Michael
Published: December 2007

Background

Cholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness.

Methods

GE of 100 mL of Ensure® meal (106 kcal, 21% fat) was measured using a 13C-octanoate breath test in 39 mechanically ventilated, critically ill patients (24 males; 55.8 ± 2.7 years old). Breath samples for 13CO2 levels were collected over the course of 4 hours, and the GE coefficient (GEC) (normal = 3.2 to 3.8) was calculated. Measurements of plasma CCK, PYY, and glucose concentrations were obtained immediately before and at 60 and 120 minutes after administration of Ensure.

Results

GE was delayed in 64% (25/39) of the patients. Baseline plasma CCK (8.5 ± 1.0 versus 6.1 ± 0.4 pmol/L; P = 0.045) and PYY (22.8 ± 2.2 versus 15.6 ± 1.3 pmol/L; P = 0.03) concentrations were higher in patients with delayed GE and were inversely correlated with GEC (CCK: r = -0.33, P = 0.04, and PYY: r = -0.36, P = 0.02). After gastric Ensure, while both plasma CCK (P = 0.03) and PYY (P = 0.02) concentrations were higher in patients with delayed GE, there was a direct relationship between the rise in plasma CCK (r = 0.40, P = 0.01) and PYY (r = 0.42, P < 0.01) from baseline at 60 minutes after the meal and the GEC.

Conclusion

In critical illness, there is a complex interaction between plasma CCK, PYY, and GE. Whilst plasma CCK and PYY correlated moderately with impaired GE, the pathogenetic role of these gut hormones in delayed GE requires further evaluation with specific antagonists.
Orbitofrontal Cortex and the Computation of Economic Value
Authors: PADOA‐SCHIOPPA CAMILLO
Published: December 2007

Abstract:Economic choice is the behavior observed when individuals select one of many available options solely based on subjective preferences. Behavioral evidence suggests that economic choice entails two mental processes: values are first assigned to the available options, and a decision is subsequently made between these values. Numerous reports show that lesions to the orbitofrontal cortex (OFC) lead to choice deficits in various domains, and imaging studies indicate that the OFC activates when people make choices. In this chapter, we review evidence from single cell recordings linking the OFC more specifically to valuation. Individual neurons in the OFC encode the value that monkeys assign to different beverages when they choose between them. These neurons encode economic value as a subjective quantity. Most importantly, neurons in the OFC encode economic valueper se, not as a modulation of sensory or motor processes. This trait distinguishes the value representation in the OFC from that observed in other brain areas. That OFC neurons encode economic value independently of visuomotor contingencies suggests that economic choice is fundamentally a choice between goods (good‐based model) rather than a choice between actions (action‐based model).
Interactions between the Orbitofrontal Cortex and the Hippocampal Memory System during the Storage of Long‐Term Memory
Authors: RAMUS SETH J. , DAVIS JENA B , DONAHUE RACHEL J , DISCENZA CLAIRE B , WAITE ALISSA A.
Published: December 2007

Abstract:  It has been proposed that long‐term declarative memories are ultimately stored through interactions between the hippocampal memory system and the neocortical association areas that initially processed the to‐be‐stored information. One association neocortex, the orbitofrontal cortex (OFC) is strongly and reciprocally connected with the hippocampal memory system and plays an important role in odor recognition memory in rats. We will report data from two studies: one that examined the firing of neurons in a task dependent on the parahippocampal region (PHR; including the perirhinal, postrhinal, and entrorhinal cortices), and one examined the firing of OFC neurons performing a task that is presumably dependent on the hippocampus. In the first study, we examined the role of OFC neurons in the continuous odor‐guided nonmatching to sample task. While the firing of neurons in the PHR and OFC are similar in this task, there are several notable differences that are consistent with the idea that OFC is a high‐order association cortex which interacts extensively with the PHR to store declarative memories. In the second study, we characterized the firing patterns of neurons in the OFC rats performing a passive, 8‐odor‐sequence memory task. Most interesting were neurons that fired selectively in anticipation of specific odors. We found that hippocampal lesions abolished the anticipatory firing in OFC, suggesting that these anticipatory responses (memory) were in fact dependent on the hippocampus, further supporting the view that the OFC interacts with the hippocampal memory system to store long‐term, declarative memories.
Hindbrain Administration of Estradiol Inhibits Feeding and Activates Estrogen Receptor-α-Expressing Cells in the Nucleus Tractus Solitarius of Ovariectomized Rats
Authors: Thammacharoen Sumpun , Lutz Thomas A. , Geary Nori , Asarian Lori
Published: December 2007

17β-Estradiol (E2), acting via estrogen receptor (ER)-α, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERα-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 μg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of 3H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERα-positive cells in the cNTS after ip injection of 4 μg/kg CCK-8. We conclude that E2, acting via ERα in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding.
The Regulation and Function of the Forkhead Transcription Factor, Forkhead Box O1, Is Dependent on the Progesterone Receptor in Endometrial Carcinoma
Authors: Ward Erin C. , Hoekstra Anna V. , Blok Leen J. , Hanifi-Moghaddam P. , Lurain John R. , Singh Diljeet K. , Buttin Barbara M. , Schink Julian C. , Kim J. Julie
Published: December 2007

In many type I endometrial cancers, the PTEN gene is inactivated, which ultimately leads to constitutively active Akt and the inhibition of Forkhead box O1 (FOXO1), a member of the FOXO subfamily of Forkhead/winged helix family of transcription factors. The expression, regulation, and function of FOXO1 in endometrial cancer were investigated in this study. Immunohistochemical analysis of 49 endometrial tumor tissues revealed a decrease of FOXO1 expression in 95.9% of the cases compared with the expression in normal endometrium. In four different endometrial cancer cell lines (ECC1, Hec1B, Ishikawa, and RL95), FOXO1 mRNA was expressed at similar levels; however, protein levels were low or undetectable in Ecc1, Ishikawa, and RL95 cells. Using small interfering RNA technology, we demonstrated that the low levels of FOXO1 protein were due to the involvement of Skp2, an oncogenic subunit of the Skp1/Cul1/F-box protein ubiquitin complex, given that silencing Skp2 increased FOXO1 protein expression in Ishikawa cells. Inhibition of Akt in Ishikawa cells also increased nuclear FOXO1 protein levels. Additionally, progestins increased FOXO1 protein levels, specifically through progesterone receptor B (PRB) as determined by using stably transfected PRA-specific and PRB-specific Ishikawa cell lines. Finally, overexpression of triple mutant (Tm) FOXO1 in the PR-specific Ishikawa cell lines caused cell cycle arrest and significantly decreased proliferation in the presence and absence of the progestin, R5020. Furthermore, TmFOXO1 overexpression induced apoptosis in PRB-specific cells in the presence and absence of ligand. Taken together, these data provide insight into the phosphoinositide-3-kinase/Akt/FOXO pathway for the determination of progestin responsiveness and the development of alternate therapies for endometrial cancer.