bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenecteplase for ST-elevation myocardial infarction in a patient treated with drotrecogin alfa (activated) for severe sepsis: a case report
Authors: Barra Lillian , Shum Jeffrey , Pickering J Geoffrey , Kao Raymond 
Published: November 2009

Abstract

Introduction
Drotrecogin alfa (activated) (DrotAA), an activated protein C, promotes fibrinolysis in patients with severe sepsis. There are no reported cases or studies that address the diagnosis and treatment of myocardial infarction in septic patients treated with DrotAA.

Case presentation
A 59-year-old Caucasian man with septic shock secondary to community-acquired pneumonia treated with DrotAA, subsequently developed an ST-elevation myocardial infarction 12 hours after starting DrotAA. DrotAA was stopped and the patient was given tenecteplase thrombolysis resulting in complete resolution of ST-elevation and no adverse bleeding events. DrotAA was restarted to complete the 96-hour course. The sepsis resolved and the patient was discharged from hospital.

Conclusion
In patients with severe sepsis or septic shock complicated by myocardial infarction, it is difficult to determine if the myocardial infarction is an isolated event or caused by the sepsis process. The efficacy and safety of tenecteplase thrombolysis in septic patients treated with DrotAA need further study.
Congenital leptin deficiency and thyroid function
Authors: Paz-Filho Gilberto , Delibasi Tuncay , Erol Halil K , Wong Ma-Li , Licinio Julio 
Published: November 2009

Abstract
Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40), before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin). The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function.

Trial Registration

ClinicalTrials.gov Identifiers: NCT00659828 and NCT00657605
ICOS promotes IL-17 synthesis in colonic intraepithelial lymphocytes in IL-10−/− mice
Authors: Schaefer Jeremy S , Montufar-Solis Dina , Vigneswaran Nadarajah , Klein John R 
Published: November 2009

AbstractIL-23 and IL-10 have opposing effects on IL-17 synthesis by mouse ICOS+ T cells in the colonic epithelium.In the absence of IL-10, colonic inflammation ensues, which is characterized by high levels of IL-17. Here, we demonstrate a direct correlation between ICOS expression and IL-17 production in cIELs. IL-10−/− mice had increased numbers of cIELs and greater colon weight. Although the CD69 early activation antigen was expressed on cIELs from normal and IL-10−/− mice, ICOS was expressed only on cIELs from IL-10−/− mice. IL-17-producing cells in IL-10−/− mice consisted of CD4+ and CD8+ cIELs; however, CD4+ cells were the predominant IL-17-producing cell population. Culture of cIELs from IL-10−/− mice with IL-23 resulted in an increase in ICOS and IL-17 expression, whereas IL-10 suppressed expression of ICOS and IL-17. This occurred in primary cultures and recall stimulation experiments. The ICOS ligand B7RP-1 was up-regulated on colonic epithelial cells and on a population of large granular leukocytes during inflammation. Culture of cIELs with B7RP-1+ DCs enhanced IL-17A production from normal cIELs but failed to do so using cIELs from ICOS−/− mice. In vivo treatment of IL-10−/− mice with antibody to ICOS resulted in a significant reduction in colonic pathology. These findings implicate ICOS as an activational signal of Th17 cells during chronic intestinal inflammation, and they suggest that under some conditions, control of ICOS expression may help to suppress chronic intestinal inflammation.
Syk expression in peripheral blood leukocytes, CD34+ progenitors, and CD34-derived basophils
Authors: Ishmael Susan S , MacGlashan Donald W 
Published: November 2009

Abstract
The critical signaling kinase of IgE-mediated reactions, syk, can be down-regulated in maturing basophils by chronic ag-gregation without altering their expression of FcRI, granule staining, and histamine content.
In human basophils from different subjects, maximum IgE-mediated histamine release and the level of syk protein expression correlate well. It is not clear when in the basophil’s lifetime the set-point for syk expression is reached or how expression levels are determined for a given individual. An examination of syk expression in peripheral blood eosinophils, neutrophils, monocytes, B and T cells, DCs, and NK cells showed that with the exception of T cells, basophils were unique in expressing low levels of syk. No correlations were observed between syk expression in basophils and other types of leukocytes, suggesting a unique mechanism of regulation for basophils. The expression level of syk in CD34+ progenitors was ∼11-fold higher than in peripheral blood basophils, and it remained at this level during maturation of the cells in IL-3 to a cell with characteristics of peripheral blood basophils. Down-regulation of syk expression in the culture-derived basophils was induced by culturing under conditions of chronic aggregation of FcεRI. Syk was down-regulated to peripheral blood basophil levels in 50% of the cells. Despite the chronic aggregation of FcεRI, the cells retained the same expression of FcεRI, histamine content, and morphological staining of granules as cells not experiencing chronic aggregation. These results suggest that chronic stimulation through FcεRI during basophil maturation might be a mechanism for down-regulating syk expression, while retaining other characteristics associated with mature peripheral blood basophils.
Adenosine A2A receptor activation limits graft-versus-host disease after allogenic hematopoietic stem cell transplantation
Authors: Lappas Courtney M , Liu Po-Ching , Linden Joel , Kang Elizabeth M , Malech Harry L 
Published: November 2009

Abstract
The selective activation of the A2A has therapeutic potential in both the prevention and treatment of acute GVHD.
GVHD is a major barrier to broader use of allogenic HSCT for nonmalignancy clinical applications such as the treatment of primary immunodeficiencies and hemoglobinopathies. We show in a murine model of C57BL/6J (H2-kb) → B6D2F1/J (H2-kb/d) acute GVHD that when initiated 2 days before transplant, the activation of the adenosine A2AR with the selective agonist ATL146e inhibits the weight loss and mortality associated with disease progression. Furthermore, circulating levels of proinflammatory cytokines and chemokines, including IFN-γ, IL-6, CCL2, KC, and G-CSF, are reduced significantly by 14-day ATL146e treatment. The up-regulation of CD25, CD69, and CD40L expression by donor CD4+ and CD8+ T cells is inhibited by A2AR activation; fewer CD3+ T cells are found in the liver, skin, and colon of ATL146e-treated mice as compared with vehicle-treated controls; and associated tissue injury is lessened. The delayed administration of ATL146e, beginning 9 days after HSCT, reverses GVHD-associated body weight loss successfully, and improvement is sustained for the duration of treatment. We conclude that the selective activation of the A2AR has therapeutic potential in the prevention and treatment of acute GVHD.
Phagosomal retention of Francisella tularensis results in TIRAP/Mal-independent TLR2 signaling
Authors: Cole Leah E , Laird Michelle H W , Seekatz Anna , Santiago Araceli , Jiang Zhaozhao , Barry Eileen , Shirey Kari Ann , Fitzgerald Katherine A , Vogel Stefanie N 
Published: November 2009

Abstract
Enhanced or prolonged interaction between an agonist and TLR2 can overcome the need for TIRAP.
TLR2 plays a central role in the activation of innate immunity in response to Ft, the causative agent of tularemia. We reported previously that Ft LVS elicited strong, dose-dependent NF-κB reporter activity in TLR2-expressing human embryo kidney 293 T cells and that Ft LVS-induced murine macrophage proinflammatory cytokine gene and protein expression is TLR2-dependent. We demonstrated further that Ft can signal through TLR2 from within the phagosome and that phagosomal retention of Ft leads to greatly increased expression of a subset of proinflammatory genes. The two adaptor proteins associated with TLR2-mediated signaling are MyD88 and TIRAP. Although MyD88 is absolutely required for the Ft-induced macrophage cytokine response, the requirement for TIRAP can be overcome through retention of Ft within the phagosome. TIRAP-independent signaling was observed whether Ft was retained in the phagosome as a result of bacterial mutation (LVSΔiglC) or BFA-mediated inhibition of phagosome acidification. The requirement for TIRAP in TLR2 signaling could also be overcome by increasing the concentrations of synthetic bacterial TLR2 agonists. Taken together, these data suggest that prolonging or enhancing the interaction between TLR2 and its agonist overcomes the “bridging” function ascribed previously to TIRAP.
Criminally invalid: the treatment outcome profile form for substance misuse
Authors: Luty Jason , Varughese Sabu , Easow Joby 
Published: November 2009

Aims and MethodTo audit completion of the Treatment Outcome Profile (TOP) form in individuals attending substance misuse services in England. Forms are completed at the start of treatment and every 3 months thereafter. All forms at 3-drug treatment services were inspected over 6 months.ResultsForms were inspected for 200 service users; 86% were fully completed. Two-thirds (67%) of service users had no declared funding for illicit drug use in the previous month (mean spending £988; s.e. = 149) despite denying any paid employment and criminal activity.Clinical ImplicationsThe section on crime in the TOP form is unreliable and completely invalid.
Associations between Common Genetic Polymorphisms in Angiopoietin-Like Proteins 3 and 4 and Lipid Metabolism and Adiposity in European Adolescents and Adults
Authors: Legry Vanessa , Bokor Szilvia , Cottel Dominique , Beghin Laurent , Catasta Giovina , Nagy Eniko , Gonzalez-Gross Marcela , Spinneker Andre , Stehle Peter , Molnár Dénes , Moreno Luis A. , Amouyel Philippe , Dallongeville Jean , Meirhaeghe Aline 
Published: November 2009

Context: Plasma-borne angiopoietin-like proteins (ANGPTL) act as endocrine factors on their target tissues. Because ANGPTL3 and ANGPTL4 play important roles in lipid metabolism and the regulation of adiposity in mice, we hypothesized that genetic variability at the ANGPTL3 and ANGPTL4 genes loci might influence lipid metabolism and fat deposition in humans.
Objective: The aim of the study was to examine the association between ANGPTL3 and ANGPTL4 genetic polymorphisms and metabolic phenotypes in adolescent and adult samples.
Design and Participants: Two independent population-based studies, one composed of 1144 adolescents (mean age, 14.8 ± 1.4 yr) from nine European countries (the HELENA study) and the other composed of 1155 adults (age range, 35–65 yr) from Northern France (the MONICA Lille study), were genotyped for one ANGPTL3 polymorphism and four ANGPTL4 polymorphisms.
Results: The ANGPTL3 rs11207997 polymorphism (minor allele frequency, 0.32) was associated with lower plasma HDL-cholesterol and apolipoprotein A-I levels in both adolescents (P = 0.0004, P = 0.00006, respectively) and adults (P = 0.03, P = 0.02, respectively). The ANGPTL4 rs4076317 polymorphism (minor allele frequency, 0.29) was associated with a higher percentage of body fat (P = 0.02) in adolescents and a higher waist-to-hip ratio (in interaction with the peroxisome proliferator-activated receptor γ Pro12Ala polymorphism) in adults (P = 0.0004).
Conclusion: The present study underlines the role of ANGPTL3 in HDL-cholesterol metabolism as early as in adolescence. Our data also suggest possible associations between ANGPTL4 polymorphisms and body fat, but these findings require replication.
Age- and gender-related differences in the geometric properties and biomechanical significance of intracortical porosity in the distal radius and tibia
Authors: Burghardt Andrew J , Kazakia Galateia J , Ramachandran Sweta , Link Thomas M , Majumdar Sharmila 
Published: November 2009

Abstract
Cortical bone contributes the majority of overall bone mass and bears the bulk of axial loads in the peripheral skeleton. Bone metabolic disorders often are manifested by cortical microstructural changes via osteonal remodeling and endocortical trabecularization. The goal of this study was to characterize intracortical porosity in a cross-sectional patient cohort using novel quantitative computational methods applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the distal radius and tibia. The distal radius and tibia of 151 subjects (57 male, 94 female; 47 ± 16 years of age, range 20 to 78 years) were imaged using HR-pQCT. Intracortical porosity (Ct.Po) was calculated as the pore volume normalized by the sum of the pore and cortical bone volume. Micro–finite element analysis (µFE) was used to simulate 1% uniaxial compression for two scenarios per data set: (1) the original structure and (2) the structure with intracortical porosity artificially occluded. Differential biomechanical indices for stiffness (ΔK), modulus (ΔE), failure load (ΔF), and cortical load fraction (ΔCt.LF) were calculated as the difference between original and occluded values. Regression analysis revealed that cortical porosity, as depicted by HR-pQCT, exhibited moderate but significant age-related dependence for both male and female cohorts (radius ρ = 0.7; tibia ρ = 0.5; p &lt; .001). In contrast, standard cortical metrics (Ct.Th, Ct.Ar, and Ct.vBMD) were more weakly correlated or not significantly correlated with age in this population. Furthermore, differential µFE analysis revealed that the biomechanical deficit (ΔK) associated with cortical porosity was significantly higher for postmenopausal women than for premenopausal women (p &lt; .001). Finally, porosity-related measures provided the only significant decade-wise discrimination in the radius for females in their fifties versus females in their sixties (p &lt; .01). Several important conclusions can be drawn from these results. Age-related differences in cortical porosity, as detected by HR-pQCT, are more pronounced than differences in standard cortical metrics. The biomechanical significance of these structural differences increases with age for men and women and provides discriminatory information for menopause-related bone quality effects. © 2010 American Society for Bone and Mineral Research
The Effect of Air Cavity Convection on the Wetting and Drying Behavior of Wood-Frame Walls Using a Multi-Physics Approach
Authors: Karagiozis Achilles N. , Kuenzel Hartwig M. 
Published: November 2009

Abstract
The moisture performance of building envelope systems are strongly dependent on the materials used, the workmanship, and the exposure loads from the interior and exterior environments. The authors have long recognized the need to include the effects of exterior cladding ventilation in the predictive capability of software tools used for hygrothermal analysis. Exterior cladding ventilation has been studied, but no conclusive recommendations have been generated until recently (Burnett, E., Straube, J., and Karagiozis, A., “Synthesis Report and Guidelines,” ASHRAE TRP-1091 Report No. 12, Nov. 2004). While the physics describing the thermal and moisture transport in the presence of air convection is understood, the pressure dynamics is still somewhat qualitatively known. With the addition of new literature data and available field generated monitored data, a simplified model for the wall air cavity ventilation was developed. The scientific approach followed initially included the benchmarking of multi-dimensional advanced hygrothermal model with laboratory and field data. The flow was understood for a wide range of exterior loadings, and once this was completed, an attempt to reduce the complex three-dimensional air flow characteristics into a simple one-dimensional analogue was made. The paper describes how this important feature was included into the WUFI-4.1 software. The paper also describes how users may employ this feature in hygrothermal designs to investigate the advantages and disadvantages of cavity ventilation. Results are also presented on the hygrothermal performance of two walls, one ventilated and the other is unvented. Results show that major differences were predicted and the wall with the ventilation cavity dried out nearly five times faster than the wall without the ventilation. Field monitored stucco wall systems with and without cavity ventilation are also included compared to the prediction provided by the hygrothermal model. Good agreement is shown between the field and WUFI 4.1 model.
Malodor as a Trigger of Stress and Negative Mood in Neighbors of Industrial Hog Operations
Authors: Horton Rachel Avery , Wing Steve , Marshall Stephen W. , Brownley Kimberly A. 
Published: November 2009

Objectives. We evaluated malodor and air pollutants near industrial hog operations as environmental stressors and negative mood triggers. Methods. We collected data from 101 nonsmoking adults in 16 neighborhoods within 1.5 miles of at least 1 industrial hog operation in eastern North Carolina. Participants rated malodor intensity, stress, and mood for 2 weeks while air pollutants were monitored. Results. Reported malodor was associated with stress and 4 mood states; odds ratios (ORs) for a 1-unit change on the 0-to-8 odor scale ranged from 1.31 (95% confidence interval [CI] = 1.16, 1.50) to 1.81 (95% CI = 1.63, 2.00). ORs for stress and feeling nervous or anxious were 1.18 (95% CI = 1.08, 1.30) and 1.12 (95% CI = 1.03, 1.22), respectively, for a 1 ppb change in hydrogen sulfide and 1.06 (95% CI = 1.00, 1.11) and 1.10 (95% CI = 1.03, 1.17), respectively, for a 1 μg/m3 change in semivolatile particulate matter less than 10 μm in aerodynamic diameter (PM10). Conclusions. Hog odor, hydrogen sulfide, and semivolatile PM10 are related to stress and negative mood in disproportionately low-income communities near industrial hog operations in eastern North Carolina. Malodor should be considered in studies of health impacts of environmental injustice.
“Pesticides Protect the Fruit, but Not the People”: Using Community-Based Ethnography to Understand Farmworker Pesticide-Exposure Risks
Authors: Snipes Shedra Amy , Thompson Beti , O'Connor Kathleen , Shell-Duncan Bettina , King Denae , Herrera Angelica P. , Navarro Bridgette 
Published: November 2009

Objectives. We used community-based ethnography and public health risk assessment to assess beliefs about pesticide exposure risks among farmworkers in the Lower Yakima Valley of Washington State. Methods. We used unstructured and semistructured interviews, work-site observation, and detailed field notes to gather data on pesticide exposure risks from 99 farmworkers. Results. Farmworkers' pesticide-relevant beliefs and attitudes could be grouped into 5 major themes: (1) dry pesticides are often perceived as a virtually harmless powder, (2) farmworkers who identify themselves as allergic to pesticides are more acutely affected by exposure, (3) the effect of pesticide exposure is more severe for those perceived as physically weak, (4) protective equipment is used selectively in response to financial pressure to work rapidly, and (5) some farmworkers delay decontamination until they find water deemed an appropriate temperature for handwashing. Conclusions. We elucidated farmworkers' pesticide-relevant beliefs regarding perceived danger and susceptibility to pesticides, the need to put safety second to financial considerations, and reasons for delaying decontamination. Researchers and policymakers should incorporate these data in study designs and legislation concerned with farmworker exposure to pesticides.
Alcohol Advertising on Boston's Massachusetts Bay Transportation Authority Transit System: An Assessment of Youths' and Adults' Exposure
Authors: Nyborn Justin A. , Wukitsch Kimberly , Nhean Siphannay , Siegel Michael 
Published: November 2009

Objectives. We investigated the frequency with which alcohol advertisements appeared on Massachusetts Bay Transportation Authority (MBTA) transit lines in Boston, MA, and we calculated adult and youths' exposure to the ads. Methods. We measured the nature and extent of alcohol advertisements on 4 Boston transit lines on 2 separate weekdays 1 month apart in June and July of 2008. We calculated weekday ad exposure for all passengers (all ages) and for Boston Public School student passengers (aged 11–18 years). Results. Alcohol ads were viewed an estimated 1 212 960 times across all Boston-area transit passengers during an average weekday, reaching the equivalent of 42.7% of that population. Alcohol ads were viewed an estimated 18 269 times by Boston Public School student transit passengers during an average weekday, reaching the equivalent of 54.1% of that population. Conclusions. Advertisers reached the equivalent of half of all Boston Public School transit passengers aged 11 to 18 years and the equivalent of nearly half of all transit passengers in the Boston area with an alcohol advertisement each day. Because of the high exposure of underage youths to alcohol advertisements, we recommend that the MBTA prohibit alcohol advertising on the Boston transit system.
Transferring Knowledge About Human Subjects Protections and the Role of Institutional Review Boards in a Community-Based Participatory Research Project
Authors: Hyatt Raymond R. , Gute David M. , Pirie Alex , Page Helen , Vasquez Ismael , Dalembert Franklin 
Published: November 2009

Among the first tasks in a collaboration between Tufts University and community organizations in Somerville, MA, was designing an interview instrument to assess occupational health needs among immigrant workers. Human subjects protections was a critical issue, but community partners were not well informed about the need for such protections or the role of the institutional review board (IRB). During research meetings, members of the team from Tufts trained community collaborators to work with research participants and organized a presentation by a key university IRB administrator. We present findings from the process evaluation of this project and suggest ways to (1) assess community partners' understanding about working with research volunteers, (2) train collaborators, and (3) involve IRBs.