bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons
Authors: Park Kiwon , Scott Alan L 
Published: August 2010

Abstract
TLR-mediated induction of cholesterol 25-hydoxylase transcription in dendritic cells and macrophages is dependent on IFN-α/IFN-β and signaling through INF-αR and STAT1.
The oxysterol-producing enzyme CH25H plays an important role in regulating lipid metabolism, gene expression, and immune activation. In vitro experiments using a panel of TLR agonists to activate BMDCs and macrophages demonstrated that Ch25h expression is induced rapidly, selectively, and robustly by the TLR ligands poly I:C and LPS. The mechanism of TLR3- and TLR4-induced transcription levels of Ch25h relies on the TRIF-mediated production of type I IFNs and requires signaling through the IFNαR and JAK/STAT1 pathway. Treatment of BMDCs and macrophages with IFN-α or IFN-β induces Ch25h in a STAT1-dependent manner. IFN-γ also up-regulated Ch25h expression by signaling through STAT1, suggesting that multiple pathways regulate the production of this enzyme. In addition, we demonstrated that regulation of Ch25h expression in vivo in lung-derived DCs and macrophages is dependent on signaling through the IFNαR and STAT1. The results suggest that the rapid induction of Ch25h and subsequent oxysterol synthesis may represent a component of the regulatory network that modulates the magnitude of innate immune reactions and possibly the nature and intensity of subsequent adaptive responses.
Disease-specific, neurosphere-derived cells as models for brain disorders
Authors: Matigian Nicholas , Abrahamsen Greger , Sutharsan Ratneswary , Cook Anthony L. , Vitale Alejandra M. , Nouwens Amanda , Bellette Bernadette , An Jiyuan , Anderson Matthew , Beckhouse Anthony G. , Bennebroek Maikel , Cecil Rowena , Chalk Alistair M. , Cochrane Julie , Fan Yongjun , Féron François , McCurdy Richard , McGrath John J. , Murrell Wayne , Perry Chris , Raju Jyothy , Ravishankar Sugandha , Silburn Peter A. , Sutherland Greg T. , Mahler Stephen , Mellick George D. , Wood Stephen A. , Sue Carolyn M. , Wells Christine A. , Mackay-Sim Alan 
Published: August 2010

SUMMARY
There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson’s disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson’s disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.
Academic self‐handicapping: Relationships with learning specific and general self‐perceptions and academic performance over time
Authors: Gadbois Shannon A. , Sturgeon Ryan D. 
Published: August 2010

Background. Academic self‐handicapping (ASH) tendencies, strategies students employ that increase their chances of failure on assessments while protecting self‐esteem, are correlated with classroom goal structures and to learners' general self‐perceptions and learning strategies. In particular, greater ASH is related to poorer academic performance but has yet to be examined with respect to learners' performance across a series of tests. Aims. This research was designed to examine the relationship between students' ASH tendencies and their self‐concept clarity, learning strategies, and performance on a series of tests in a university course. Sample. A total of 209 (153 female; 56 male) Canadian university psychology students participated in this study. Methods. Participants' ASH tendencies, self‐concept clarity, approaches to learning, and self‐regulatory learning strategies were assessed along with expected grades and hours of study in the course from which they were recruited. Finally, students' grades were obtained for the three tests for the course from which they were recruited. Results. Students reporting greater self‐handicapping tendencies reported lower self‐concept clarity, lower academic self‐efficacy, greater test anxiety, more superficial learning strategies, and scored lower on all tests in the course. The relationships of ASH scores and learner variables with performance varied across the three performance indices. In particular, ASH scores were more strongly related to second and third tests, and prior performances were accounted for. ASH scores accounted for a relatively small but significant proportion of variance for all three tests. Conclusions. These results showed that ASH is a unique contributing factor in student performance outcomes, and may be particularly important after students complete the initial assessment in a course.
A feasibility study of mindfulness‐based cognitive therapy for individuals with borderline personality disorder
Authors: Sachse Sandy , Keville Saskia , Feigenbaum Janet 
Published: August 2010

Objectives. Mindfulness‐based cognitive therapy (MBCT) was originally developed to prevent relapse in recurrent depression. More recently it has been applied to individuals at high risk of suicide or currently suffering with anxiety and depression. The aim of this study was to consider the feasibility of MBCT for individuals with a diagnosis of borderline personality disorder (BPD). Design. The design of the study was a repeated measures, quasi‐experimental design employing within‐subject and between‐subject comparisons of a sample of participants with BPD. Based on previous studies and theoretical models of the effect of mindfulness and of cognitive therapy, pre‐ and post‐group measures of mindfulness, depression, anxiety, dissociation, impulsivity, experiential avoidance, and attention were obtained. Method. Participants attended an 8‐week adapted MBCT (MBCT‐a) group intervention. A total of 22 participants were assessed pre‐ and post‐intervention and were subsequently divided for analysis into two groups: treatment completers (N= 16) and non‐completers (number of sessions attended < 4; N= 6). Results. The study found that MBCT‐a is acceptable to individuals with BPD. Using intention to treat analyses, only attentional control improved. However, post hoc analyses of treatment improvers (N= 9) identified changes in mindfulness and somatoform dissociation. A dose‐effect analysis suggested a weak improvement in mindfulness, experiential avoidance, state anxiety, and somatoform dissociation. Conclusions. This study suggests that further exploration of MBCT for use with individuals with BPD is merited. The study lends tentative support for attentional and avoidance models of the effects of mindfulness.
In search of a framework for the treatment of alexithymia
Authors: Vanheule Stijn , Verhaeghe Paul , Desmet Mattias 
Published: August 2010

Purpose. Clinical observations and controlled studies indicate that the treatment of alexithymic patients is most difficult. Moreover, stronger degrees of alexithymia predict worse therapy outcome. We argue that in order to make therapy for alexithymia‐related disorders fruitful, a conceptualization of alexithymia in terms of interpersonally imbedded affect regulation is needed. Methods and results. Based on a re‐interpretation of Freud's actual neurosis via Lacan's theory and contemporary attachment theory, we present a theoretical framework that incorporates these points. This framework helps us to explain why classic psychotherapeutic approaches fail, and to formulate principles for an alternative psychoanalytic therapeutic approach that addresses the theoretically discerned difficulties. A clinical vignette is used to examine how these principles can be implemented in clinical practice. Conclusion. Therapy with actual‐neurotic alexithymic patients should focus on distressing situations, starting from which a three‐step logic can be deployed. During therapy, mental representations on difficult situations in patients' lives need to be constructed by (1) putting into words the chain of events that makes up the distressing situation; (2) making the patient's appraisal of the difficult situation explicit; and (3) addressing affective responses and discussing the patient's way of dealing with the difficult situation.
Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients
Authors: Roemmler J , Otto B , Arafat A M , Bidlingmaier M , Schopohl J 
Published: August 2010

IntroductionPegvisomant (peg) is a GH receptor antagonist. Inde novoacromegalic patients with high GH levels, ghrelin and leptin levels are reduced, suggesting a direct GH-mediated effect. The aim of our study was to evaluate whether peg treatment in acromegalic patients may abolish the GH impact on ghrelin and leptin levels.MethodsGhrelin, leptin and endogenous GH were measured in ten peg-treated acromegalic patients (three females/seven males, 47 years (28–57)), ten patients with active (act) and ten patients with inactive disease (inact) as well as in ten gender-, age- and body mass index (BMI)-matched healthy volunteers (controls). Endogenous GH was measured using a special in-house assay without interference by peg; total ghrelin and leptin were determined using a commercial RIA and an immunofluorometric in-house assay respectively.ResultsAge and BMI did not differ significantly between groups. Endogenous GH was significantly higher in peg (6.3 μg/l (1.5–41)) and act (9.3 μg/l (1.7–70)) compared with controls (0.1 μg/l (0.1–3.1)) and inact (0.35 μg/l (0.1–2.0),P<0.001). Ghrelin was significantly higher in peg (232 ng/l (96–351)) compared with act (102 ng/l (33–232),P<0.01), whereas ghrelin was not significantly different between the other groups. Leptin was highest in controls (19 μg/l (4–57)) and lowest in act (6 μg/l (2–21)), but this difference did not reach significance.ConclusionTreatment with peg seems to disrupt the feedback loop of ghrelin and GH, leading to elevated ghrelin levels. Furthermore, peg therapy appears not to have a strong impact on leptin levels, as acromegalic patients with and without peg treatment showed similar leptin levels.
“Phillis Wheatley's First Effort”
Authors: Carretta Vincent 
Published: August 2010

Biographical Research at the Massachusetts Historical Society has Discovered in The 1773 Diary of Jeremy Belknap (1744-98), a Congregationalist clergyman, what is likely a text by Phillis Wheatley that predates any known before now. Belknap's diary is interleaved in Bickerstaff's Boston Almanack. For the Year of Our Lord, 1773. The last page includes a twenty-word poem in Belknap's hand that he identifies as “Phillis Wheatley's first Effort———-AD 1765. EE 11.” Belknap transcribes the text twice. The first version is in three lines, as if he could not decide whether it was prose or poetry, with an inserted two-word phrase placed above the first line and located by a caret below it:Unto SalvationMrsThacher's Son is gonê her Daughter tooso I concludeThey are both gone to be renewed
Excerpts from Old Solomon; or, A Slave Family in the Nineteenth Century
Authors: Testut Charles , Kim Heidi Kathleen 
Published: August 2010

Introduction: The Francophone Uncle Tom's CabinThe Overlooked American Francophone Novel Le Vieux Salomon, Ou Une Famille D'Esclaves Au XIXE Siècle (OLD SOLOMON; OR, A Slave Family in the Nineteenth Century), by Charles Testut (1819-92), offers a contemporaneous description of slavery as a global commerce with international causes and effects. The novel's geographic scope, as well as Testut's interest in contrasting the life in the French Caribbean with slavery in the United States, makes Old Solomon an ideal text through which to examine the representation of economic and cultural circulation in the Americas. Old Solomon is a clear response to Harriet Beecher Stowe's Uncle Tom's Cabin (1852), with some similar characters and situations, but is more trangressive and violent.
Enhanced Levels of microRNA-125b in Vascular Smooth Muscle Cells of Diabetic db/db Mice Lead to Increased Inflammatory Gene Expression by Targeting the Histone Methyltransferase Suv39h1
Authors: Villeneuve Louisa M. , Kato Mitsuo , Reddy Marpadga A. , Wang Mei , Lanting Linda , Natarajan Rama 
Published: August 2010

OBJECTIVE
Diabetes remains a major risk factor for vascular complications that seem to persist even after achieving glycemic control, possibly due to “metabolic memory.” Using cultured vascular smooth muscle cells (MVSMC) from type 2 diabetic db/db mice, we recently showed that decreased promoter occupancy of the chromatin histone H3 lysine-9 methyltransferase Suv39h1 and the associated repressive epigenetic mark histone H3 lysine-9 trimethylation (H3K9me3) play key roles in sustained inflammatory gene expression. Here we examined the role of microRNAs (miRs) in Suv39h1 regulation and function in MVSMC from diabetic mice.

RESEARCH DESIGN AND METHODS
We used luciferase assays with Suv39h1 3′untranslated region (UTR) reporter constructs and Western blotting of endogenous protein to verify that miR-125b targets Suv39h1. We examined the effects of Suv39h1 targeting on inflammatory gene expression by quantitative real time polymerase chain reaction (RT-qPCR), and H3K9me3 levels at their promoters by chromatin immunoprecipitation assays.

RESULTS
We observed significant upregulation of miR-125b with parallel downregulation of Suv39h1 protein (predicted miR-125b target) in MVSMC cultured from diabetic db/db mice relative to control db/+. miR-125b mimics inhibited both Suv39h1 3′UTR luciferase reporter activity and endogenous Suv39h1 protein levels. Conversely, miR-125b inhibitors showed opposite effects. Furthermore, miR-125b mimics increased expression of inflammatory genes, monocyte chemoattractant protein-1, and interleukin-6, and reduced H3K9me3 at their promoters in nondiabetic cells. Interestingly, miR-125b mimics increased monocyte binding to db/+ MVSMC toward that in db/db MVSMC, further imitating the proinflammatory diabetic phenotype. In addition, we found that the increase in miR-125b in db/db VSMC is caused by increased transcription of miR-125b-2.

CONCLUSIONS
These results demonstrate a novel upstream role for miR-125b in the epigenetic regulation of inflammatory genes in MVSMC of db/db mice through downregulation of Suv39h1.
Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
Authors: Dandona Paresh , Ghanim Husam , Bandyopadhyay Arindam , Korzeniewski Kelly , Ling Sia Chang , Dhindsa Sandeep , Chaudhuri Ajay 
Published: August 2010

OBJECTIVE
To investigate whether insulin reduces the magnitude of oxidative, nitrosative, and inflammatory stress and tissue damage responses induced by endotoxin (lipopolysaccharide [LPS]).

RESEARCH DESIGN AND METHODS
Nine normal subjects were injected intravenously with 2 ng/kg LPS prepared from Escherichia coli. Ten others were infused with insulin (2 units/h) for 6 h in addition to the LPS injection along with 100 ml/h of 5% dextrose to maintain normoglycemia.

RESULTS
LPS injection induced a rapid increase in plasma concentrations of nitric oxide metabolites, nitrite and nitrate (NOM), and thiobarbituric acid–reacting substances (TBARS), an increase in reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNLs), and marked increases in plasma free fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibition factor (MIF), C-reactive protein, resistin, visfatin, lipopolysaccharide binding protein (LBP), high mobility group-B1 (HMG-B1), and myoglobin concentrations. The coinfusion of insulin led to a total elimination of the increase in NOM, free fatty acids, and TBARS and a significant reduction in ROS generation by PMNLs and plasma MIF, visfatin, and myoglobin concentrations. Insulin did not affect TNF-α, MCP-1, IL-6, LBP, resistin, and HMG-B1 increases induced by the LPS.

CONCLUSIONS
Insulin reduces significantly several key mediators of oxidative, nitrosative, and inflammatory stress and tissue damage induced by LPS. These effects of insulin require further investigation for its potential use as anti-inflammatory therapy for endotoxemia.
Age and Sex Differences in the Clustering of Metabolic Syndrome Factors
Authors: Kuk Jennifer L. , Ardern Chris I. 
Published: August 2010

OBJECTIVE
The metabolic syndrome is a general term given to a clustering of cardiometabolic risk factors that may consist of different phenotype combinations. The purpose of this study was to determine the prevalence of the different combinations of factors that make up the metabolic syndrome as defined by the National Cholesterol Education Program and to examine their association with all-cause mortality in younger and older men and women.

RESEARCH DESIGN AND METHODS
A total of 2,784 men and 3,240 women from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up = 14.2 ± 0.2 years) were studied.

RESULTS
Metabolic syndrome was present in 26% of younger (aged ≤65 years) and 55.0% of older (aged &gt;65 years) participants. The most prevalent metabolic syndrome combination was the clustering of high triglycerides, low HDL cholesterol, and elevated blood pressure in younger men (4.8%) and triglycerides, HDL cholesterol, and elevated waist circumference in younger women (4.2%). The presence of all five metabolic syndrome factors was the most common metabolic syndrome combination in both older men (8.0%) and women (9.2%). Variation existed in how metabolic syndrome combinations were associated with mortality. In younger adults, having all five metabolic syndrome factors was most strongly associated with mortality risk, whereas in older men, none of metabolic syndrome combinations were associated with mortality. In older women, having elevated glucose or low HDL as one of the metabolic syndrome components was most strongly associated with mortality risk.

CONCLUSIONS
Metabolic syndrome is a heterogeneous entity with age and sex variation in component clusters that may have important implications for interpreting the association between metabolic syndrome and mortality risk. Thus, metabolic syndrome used as a whole may mask important differences in assessing health and mortality risk.
Restoration of Nasal Cytology after Endoscopic Turbinoplasty versus Laser-Assisted Turbinoplasty
Authors: Cassano Michele , Granieri Carla , Del Giudice Alessandro Maselli , Mora Francesco , Fiocca-Matthews Emily , Cassano Pasquale 
Published: August 2010

Background Insult from surgical trauma leads to a degeneration of the nasal epithelium, resulting in morphological–volumetric changes involving the entire cell or a specific cell component. Alterations in normal nasal mucosa were assessed by nasal cytology and other functional tests after either endoscopic turbinoplasty or laser-assisted turbinoplasty for reducing inferior turbinate enlargement. Methods A total of 150 patients with chronic nasal obstruction due to inferior turbinate hypertrophy were randomly assigned to undergo laser-assisted turbinoplasty or endoscopic turbinoplasty. Preoperative and postoperative assessment at 1 and 3 months follow-up included active anterior rhinomanometry, measurement of mucociliary transport time (MCTt), and nasal cytology to determine whether improved nasal breathing was accompanied by a restoration of preoperative nasal cytology and MCTt. One year after the operation, nasal cytology was repeated to definitively evaluate the presence of surgery-related cytological damage. Results At both postoperative visits, nasal resistance had decreased similarly in both treatment groups; mean MCTt was significantly shorter in the endoscopic turbinoplasty-treated group (p < 0.05); at both visits, the number of altered ciliated cells had increased in the laser-assisted turbinoplasty-treated group but decreased in the endoscopic turbinoplasty-treated group, which, unlike the laser-assisted turbinoplasty-treated group, was also noted to have progressed toward a significant improvement in the goblet-to-ciliated cell ratio (p < 0.01). Conclusion When compared with laser-assisted turbinoplasty, endoscopic turbinoplasty is a conservative technique for inferior turbinate reduction that allows better restoration of preoperative nasal cytology and shorter MCTt.
Biometric Predictive Models for the Evaluation of Olfactory Recovery after Endoscopic Sinus Surgery in Patients with Nasal Polyposis
Authors: Katotomichelakis Michael , Gouveris Haralampos , Tripsianis Gregory , Simopoulou Maria , Papathanassiou Jannis , Danielides Vassilios 
Published: August 2010

Background Determination of predictive factors and specific values of olfactory function after endoscopic sinus surgery (ESS) using objective diagnostic methods may support consultation of respective patients. This study was designed to assess the longitudinal olfactory functional outcome after ESS in patients with severe chronic rhinosinusitis (CRS) with nasal polyposis, to evaluate associated clinical factors and to provide statistical models for prediction of olfactory recovery. Methods One hundred sixteen patients with nasal polyposis refractory to medical treatment underwent ESS. Olfactory testing was performed preoperatively and 1, 3, and 6 months after surgery using “Sniffin’ Sticks” (Burghardt, Wedel, Germany). Using multivariate linear and logistic regression analysis, statistical models were generated to predict (i) the 6th-month composite threshold-discrimination-identification (TDI) score and (ii) the probability of attaining normal olfaction at 6 months. Results A significant stepwise increment of all olfactory function indices was found over time. Factors influencing final olfactory recovery were patients’ age, duration of olfactory deficit, previous paranasal sinus surgery, and aspirin-exacerbated respiratory disease. The first model explained 70% of the observed variation in postoperative TDI scores. The second model correctly classified 76% of the patients. Conclusion A significant progressive improvement of olfaction for at least 6 months was observed after ESS. The statistical models developed may be useful for consultation of ESS candidates in clinical practice.