bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial Lipoprotein TLR2 Agonists Broadly Modulate Endothelial Function and Coagulation Pathways In Vitro and In Vivo
Authors: Shin Hae-Sook , Xu Fengyun , Bagchi Aranya , Herrup Elizabeth , Prakash Arun , Valentine Catherine , Kulkarni Hrishikesh , Wilhelmsen Kevin , Warren Shaw , Hellman Judith 
Published: December 2010

Abstract
TLR2 activation induces cellular and organ inflammation and affects lung function. Because deranged endothelial function and coagulation pathways contribute to sepsis-induced organ failure, we studied the effects of bacterial lipoprotein TLR2 agonists, including peptidoglycan-associated lipoprotein, Pam3Cys, and murein lipoprotein, on endothelial function and coagulation pathways in vitro and in vivo. TLR2 agonist treatment induced diverse human endothelial cells to produce IL-6 and IL-8 and to express E-selectin on their surface, including HUVEC, human lung microvascular endothelial cells, and human coronary artery endothelial cells. Treatment of HUVEC with TLR2 agonists caused increased monolayer permeability and had multiple coagulation effects, including increased production of plasminogen activator inhibitor-1 (PAI-1) and tissue factor, as well as decreased production of tissue plasminogen activator and tissue factor pathway inhibitor. TLR2 agonist treatment also increased HUVEC expression of TLR2 itself. Peptidoglycan-associated lipoprotein induced IL-6 production by endothelial cells from wild-type mice but not from TLR2 knockout mice, indicating TLR2 specificity. Mice were challenged with TLR2 agonists, and lungs and plasmas were assessed for markers of leukocyte trafficking and coagulopathy. Wild-type mice, but not TLR2 mice, that were challenged i.v. with TLR2 agonists had increased lung levels of myeloperoxidase and mRNAs for E-selectin, P-selectin, and MCP-1, and they had increased plasma PAI-1 and E-selectin levels. Intratracheally administered TLR2 agonist caused increased lung fibrin levels. These studies show that TLR2 activation by bacterial lipoproteins broadly affects endothelial function and coagulation pathways, suggesting that TLR2 activation contributes in multiple ways to endothelial activation, coagulopathy, and vascular leakage in sepsis.
Lactobacillus-Mediated Priming of the Respiratory Mucosa Protects against Lethal Pneumovirus Infection
Authors: Gabryszewski Stanislaw J. , Bachar Ofir , Dyer Kimberly D. , Percopo Caroline M. , Killoran Kristin E. , Domachowske Joseph B. , Rosenberg Helene F. 
Published: December 2010

Abstract
The inflammatory response to respiratory virus infection can be complex and refractory to standard therapy. Lactobacilli, when targeted to the respiratory epithelium, are highly effective at suppressing virus-induced inflammation and protecting against lethal disease. Specifically, wild-type mice primed via intranasal inoculation with live or heat-inactivated Lactobacillus plantarum or Lactobacillus reuteri were completely protected against lethal infection with the virulent rodent pathogen, pneumonia virus of mice; significant protection (60% survival) persisted for at least 13 wk. Protection was not unique to Lactobacillus species, and it was also observed in response to priming with nonpathogenic Gram-positive Listeria innocua. Priming with live lactobacilli resulted in diminished granulocyte recruitment, diminished expression of multiple proinflammatory cytokines (CXCL10, CXCL1, CCL2, and TNF), and reduced virus recovery, although we have demonstrated clearly that absolute virus titer does not predict clinical outcome. Lactobacillus priming also resulted in prolonged survival and protection against the lethal sequelae of pneumonia virus of mice infection in MyD88 gene-deleted (MyD88−/−) mice, suggesting that the protective mechanisms may be TLR-independent. Most intriguing, virus recovery and cytokine expression patterns in Lactobacillus-primed MyD88−/− mice were indistinguishable from those observed in control-primed MyD88−/− counterparts. In summary, we have identified and characterized an effective Lactobacillus-mediated innate immune shield, which may ultimately serve as critical and long-term protection against infection in the absence of specific antiviral vaccines.
Genome-Based In Silico Identification of New Mycobacterium tuberculosis Antigens Activating Polyfunctional CD8+ T Cells in Human Tuberculosis
Authors: Tang Sheila T. , van Meijgaarden Krista E. , Caccamo Nadia , Guggino Giuliana , Klein Michèl R. , van Weeren Pascale , Kazi Fatima , Stryhn Anette , Zaigler Alexander , Sahin Ugur , Buus Søren , Dieli Francesco , Lund Ole , Ottenhoff Tom H. M. 
Published: December 2010

Abstract
Although CD8+ T cells help control Mycobacterium tuberculosis infection, their M. tuberculosis Ag repertoire, in vivo frequency, and functionality in human tuberculosis (TB) remains largely undefined. We have performed genome-based bioinformatics searches to identify new M. tuberculosis epitopes presented by major HLA class I supertypes A2, A3, and B7 (covering 80% of the human population). A total of 432 M. tuberculosis peptides predicted to bind to HLA-A*0201, HLA-A*0301, and HLA-B*0702 (representing the above supertypes) were synthesized and HLA-binding affinities determined. Peptide-specific CD8+ T cell proliferation assays (CFSE dilution) in 41 M. tuberculosis-responsive donors identified 70 new M. tuberculosis epitopes. Using HLA/peptide tetramers for the 18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides, recognition by cured TB patients’ CD8+ T cells was validated for all 18 epitopes. Intracellular cytokine staining for IFN-γ, IL-2, and TNF-α revealed mono-, dual-, as well as triple-positive CD8+ T cells, indicating these M. tuberculosis peptide-specific CD8+ T cells were (poly)functional. Moreover, these T cells were primed during natural infection, because they were absent from M. tuberculosis-noninfected individuals. Control CMV peptide/HLA-A*0201 tetramers stained CD8+ T cells in M. tuberculosis-infected and noninfected individuals equally, whereas Ebola peptide/HLA-A*0201 tetramers were negative. In conclusion, the M. tuberculosis-epitope/Ag repertoire for human CD8+ T cells is much broader than hitherto suspected, and the newly identified M. tuberculosis Ags are recognized by (poly)functional CD8+ T cells during control of infection. These results impact on TB-vaccine design and biomarker identification.
Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes
Authors: Jagannathan-Bogdan Madhumita , McDonnell Marie E. , Shin Hyunjin , Rehman Qasim , Hasturk Hatice , Apovian Caroline M. , Nikolajczyk Barbara S. 
Published: December 2010

Abstract
An appropriate balance between proinflammatory (Th17 and Th1) and anti-inflammatory (regulatory T cells [Tregs] and Th2) subsets of T cells is critical to maintain homeostasis and avoid inflammatory disease. Type 2 diabetes (T2D) is a chronic inflammatory disease promoted by changes in immune cell function. Recent work indicates T cells are important mediators of inflammation in a mouse model of T2D. These studies identified an elevation in the Th17 and Th1 subsets with a decrease in the Treg subset, which culminates in inflammation and insulin resistance. Based on these data, we tested the hypothesis that T cells in T2D patients are skewed toward proinflammatory subsets. Our data show that blood from T2D patients has increased circulating Th17 cells and elevated activation of Th17 signature genes. Importantly, T cells required culture with monocytes to maintain Th17 signatures, and fresh ex vivo T cells from T2D patients appeared to be poised for IL-17 production. T cells from T2D patients also have increased production of IFN-γ, but produce healthy levels of IL-4. In contrast, T2D patients had decreased percentages of CD4+ Tregs. These data indicate that T cells in T2D patients are naturally skewed toward proinflammatory subsets that likely promote chronic inflammation in T2D through elevated cytokine production. Potential therapies targeted toward resetting this balance need to be approached with caution due to the reciprocal relationship between Th17 cells and Tregs. Understanding the unique aspects of T2D T cells is essential to predict outcomes of such treatments.
Systemic Immunological Tolerance to Ocular Antigens Is Mediated by TRAIL-Expressing CD8+ T Cells
Authors: Griffith Thomas S. , Brincks Erik L. , Gurung Prajwal , Kucaba Tamara A. , Ferguson Thomas A. 
Published: December 2010

Abstract
Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required Fas ligand-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by CD8+ regulatory T cells. This study examined the mechanism by which these CD8+ regulatory T cells mediate tolerance after AC injection of Ag. AC injection of Ag did not prime CD4+ T cells and led to increased TRAIL expression by splenic CD8+ T cells. Unlike wild-type mice, Trail−/− or Dr5−/− mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes of these mice. CD8+ T cells from Trail−/− mice that were first injected via the AC with Ag were unable to transfer tolerance to naive recipient wild-type mice, but CD8+ T cells from AC-injected wild-type or Dr5−/− mice could transfer tolerance. Importantly, the transferred wild-type (Trail+/+) CD8+ T cells were also able to decrease the number of infiltrating inflammatory cells into the eye; however, Trail−/− CD8+ T cells were unable to limit the inflammatory cell ingress. Together, our data suggest that “helpless” CD8+ regulatory T cells generated after AC injection of Ag enforce systemic tolerance in a TRAIL-dependent manner to inhibit inflammation in the eye.
Cutting Edge: Crucial Role of IL-1 and IL-23 in the Innate IL-17 Response of Peripheral Lymph Node NK1.1− Invariant NKT Cells to Bacteria
Authors: Doisne Jean-Marc , Soulard Valérie , Bécourt Chantal , Amniai Latiffa , Henrot Pauline , Havenar-Daughton Colin , Blanchet Charlène , Zitvogel Laurence , Ryffel Bernhard , Cavaillon Jean-Marc , Marie Julien C. , Couillin Isabelle , Benlagha Kamel 
Published: December 2010

Abstract
We have shown previously that peripheral lymph node-resident retinoic acid receptor-related orphan receptor γt+ NK1.1− invariant NKT (iNKT) cells produce IL-17A independently of IL-6. In this study, we show that the concomitant presence of IL-1 and IL-23 is crucial to induce a rapid and sustained IL-17A/F and IL-22 response by these cells that requires TCR–CD1d interaction and partly relies on IL-23–mediated upregulation of IL-23R and IL-1R1 expression. We further show that IL-1 and IL-23 produced by pathogen-associated molecular pattern-stimulated dendritic cells induce this response from NK1.1− iNKT cells in vitro, involving mainly TLR2/4-signaling pathways. Finally, we found that IL-17A production by these cells occurs very early and transiently in vivo in response to heat-killed bacteria. Overall, our study indicates that peripheral lymph node NK1.1− iNKT cells could be a source of innate Th17-related cytokines during bacterial infections and supports the hypothesis that they are able to provide an efficient first line of defense against bacterial invasion.
Facile synthesis of electroactive polypyrrole–chitosan composite nanospheres with controllable diameters
Authors: Li Yingmei , Li Guicun , Peng Hongrui , Chen Kezheng 
Published: December 2010

AbstractPolypyrrole–chitosan composite (PCC) nanospheres with uniform diameters have been synthesized by in situ chemical oxidation polymerization of pyrrole in chitosan aqueous solution. The influences of synthetic parameters, such as the concentrations of chitosan and pyrrole, and types of oxidants on the diameters and molecular structures of the PCC nanospheres have been investigated. It is found that the diameters of the PCC nanospheres can be controlled by adjusting the concentrations of chitosan and pyrrole. Chitosan is absorbed on/in polypyrrole nanospheres to form the PCC nanospheres. The resulting PCC nanospheres preserve both the electroactivity of polypyrrole and the biocompatibility and bioactivity of chitosan, and may have potential biomedical applications such as in biosensors and in the controlled release of drugs. Copyright © 2010 Society of Chemical Industry
Safety and Efficacy of Attempts to Reduce Shoulder Dislocations by Non-medical Personnel in the Wilderness Setting
Authors: Ditty Jack , Chisholm Dugald , Davis Stephen M. , Estelle-Schmidt Mary 
Published: December 2010

Objective The objectives of this study were to explore the success rate and the complication rate for shoulder reduction attempts by non-medical personnel in the wilderness setting, and to compare the average time to reduction for those done on scene versus those that waited for reduction at a medical facility. Methods In this study we solicited online survey responses from users of wilderness sports forums between October 2008 and April 2009. These surveys asked respondents to describe previous wilderness sports injuries they experienced. Descriptive statistics were calculated, and the Mann-Whitney U test was used to compare average reduction times, with an alpha of .05 selected as the significance threshold. Results Overall, there were 112 responses with 56 describing shoulder dislocations that were reduced either on scene or at a medical facility. Reduction on scene, in the absence of a medically trained person, was attempted in 39 of these 56 cases with a success rate of 71.8% (28/39). The median time to reduction on scene was 5 minutes, compared to 135 minutes from the time of injury for those that were reduced at a medical facility ( P <.001). Other than pain during the reduction, there were no reports of serious complications associated with the reduction attempts. Conclusions These data suggest that reduction of dislocations in the wilderness setting by non-medical personnel may be safe and effective, and significantly decreases the time to reduction. These findings may help guide future instruction of participants in high-risk wilderness sports.
Rhabdomyolysis and Hyponatremia: A Cluster of Five Cases at the 161-km 2009 Western States Endurance Run
Authors: Bruso Jessica Rose , Hoffman Martin D. , Rogers Ian R. , Lee Linda , Towle Gary , Hew-Butler Tamara 
Published: December 2010

Objective Five of 400 starters of the 2009 Western States Endurance Run (WSER) were hospitalized with hyponatremia and rhabdomyolysis. This article explores the risk factors associated with development of hyponatremia and rhabdomyolysis. Methods Data on the 5 cases were collected retrospectively from the runners and medical records, and all race participants were invited to complete a post-race survey. Characteristics of the cases were compared with the other race participants. Results The 5 runners developing hyponatremia with rhabdomyloysis were men with a mean (±SD) age of 39 ± 7 years. Presenting complaints included neurological symptoms among 3 and nausea among 3. Compared with those runners not developing hyponatremia with rhabdomyolysis, the cases tended to be younger, faster, more likely to have sustained an injury which interfered with training prior to the race, and were more likely to use nonsteroidal anti-inflammatory drugs (NSAIDs) during the race. The 3 of 5 cases progressing to acute renal failure were characterized by higher initial blood urea nitrogen (BUN; 43–69 vs 18–23 mg/dL) and creatinine (2.8–4.9 vs 1.1–1.2 mg/dL) levels but were not distinguished by creatinine phosphokinase (CPK) concentrations. Conclusions Over 1% of participants in the 2009 WSER were hospitalized with hyponatremia in combination with rhabdomyolysis. These individuals tended to be younger, faster, more likely to have had an injury that interfered with training, and more likely to have used NSAIDs during the race. Higher initial BUN and creatinine levels, but not CPK concentrations, distinguished those 3 who progressed to acute renal failure.
Accuracy of Internet Recommendations for Prehospital Care of Venomous Snake Bites
Authors: Barker Sarah , Charlton Nathan P. , Holstege Christopher P. 
Published: December 2010

Objective To evaluate the accuracy of Internet information regarding the prehospital care of venomous snake bites. Methods Two major search engines were used to identify 48 Web sites regarding 6 prehospital treatment options for snake bite (removal of constrictive devices, ice, heat, electric shock, incision, and suction). Web sites were evaluated for their quality using the Health on the Net (HON) seal and Journal of the American Medical Association ( JAMA) benchmarks. Results Of the 48 Web sites reviewed, 26 (54.1%) contained inappropriate recommendations. The remaining 22 Web sites were appropriate regarding all modalities addressed. Among the Web sites reviewed, inappropriate treatment recommendations included: suction (14); ice (6); incision (4); electric shock (1). Five Web sites that met all 4 JAMA benchmarks and the HON seal included 3 inappropriate treatment recommendations. Conversely, the 5 Web sites that met none of the JAMA benchmarks nor included the HON seal included only 2 inappropriate treatment measures. Conclusion This study highlights the variety of misinformation available on the Internet regarding prehospital care of snake bites, and the unreliability of the HON seal and JAMA benchmarks as markers of accuracy. As the Internet becomes an increasing source of medical information for both the public and clinicians, the importance of accurate Web sites becomes imperative. Clinicians and lay people should be aware of the high variability of Internet information regarding snake bite prehospital care.
Expedition Medicine—the Risk of Illness and Injury
Authors: Lyon R.M. , Wiggins C.M. 
Published: December 2010

Objective Expeditions organized by commercial companies are becoming increasingly popular. Charity expeditions take inexperienced participants on trips all over the world, with participants being sponsored to raise funds for charitable causes. The incidence of illness or injury while participating in charity expeditions is unknown. The objective of this study is to report the incidence and severity of illness and injuries occurring on worldwide charity expeditions. Methods Retrospective, observational study reviewing expedition medical reports from 232 expeditions organized by a single commercial expedition company for a 5-year period (January 1, 2004 through December 31, 2008). Results Complete expedition medical reports were available for 210 (91%) trips, involving 4077 participants over 1524 expedition days. Expeditions reported a total of 1564 incidents over 42 482 participant-days in the field, including days spent traveling to the expedition site. In 1465 (94%) cases “minor” injury or illness was recorded, 79 (5%) “moderate,” and 20 (1%) “major” in severity. No deaths were reported. Gastrointestinal upset was the commonest reported minor condition and severe acute mountain sickness the commonest major condition. Overall, the incidence per 1000 participant-days of minor illness or injury was 34.48, moderate illness or injury 1.86, and major illness or injury 0.47. Conclusion The risk of sustaining major injury or illness on an overseas charity expedition is low. The consequences of becoming injured or unwell in a remote environment can be serious, and appropriate medical care is required.
Postexercise Peripheral Oxygen Saturation After Completion of the 6-Minute Walk Test Predicts Successfully Reaching the Summit of Aconcagua
Authors: Lazio Matthew P. , Van Roo Jon D. , Pesce Carlos , Malik Sanjeev , Courtney D. Mark 
Published: December 2010

Objective The 6-minute walk test (6MWT) is a single measurement of functional status in patients with cardiovascular disease. It has not been studied at high altitude. We investigate the screening value of 6-minute walk distance (6MWD) and postexercise vital sign (VS) measurements as predictors of successfully reaching the summit or development of acute mountain sickness (AMS) on Aconcagua (6962 m). Methods Prospective observational cohort in Aconcagua Provincial Park, Argentina. Adults climbing the normal route who registered with base camp physicians were included. There were no exclusion criteria. VSs were measured before (resting) and after (postexercise) completion of 6MWT while volunteers acclimatized at Plaza de Mulas base camp (4365 m). Volunteers proceeded towards the summit at their own pace and upon descent returned a questionnaire with maximum altitude reached and Lake Louise AMS Self-report Score (LLSelf). Results One hundred twenty-four volunteers completed the 6MWT. Sixty-four volunteers (51.6%) completed questionnaires; 56% summited. Median LLSelf was 4 (IQR: 3.0–6.5). There was no association between any resting or postexercise VS measurements and AMS. However, mean postexercise SpO2 was 80.8% in summiters and 76.4% in nonsummiters, a difference of −4.4% (95% CI: −6.7 to −2.0, p = 0.0005). Postexercise SpO2 < 75% had 97.2% sensitivity and negative likelihood ratio of 0.086 in predicting the outcome of successfully reaching the summit: only one climber with SpO2 < 75% successfully reached the summit. Conclusions This study provides the first published data on 6MWD recorded in the field at high altitude. Postexercise SpO2 < 75% may be a useful screening test for predicting the outcome of successfully reaching the summit of Aconcagua.
10% Povidone-Iodine May Be a Practical Field Water Disinfectant
Authors: Heiner Jason D. , Hile David C. , Demons Samandra T. , Wedmore Ian S. 
Published: December 2010

Objective A paucity of data exists regarding the use of iodophores such as povidone-iodine (PVI) to disinfect water. We sought to determine a practical minimal disinfecting concentration of 10% PVI over different contact times and temperatures when added to water inoculated with E. coli. Methods 1:100, 1:1,000, and 1:10,000 dilutions of 10% PVI were created. Escherichia coli was exposed to these dilutions for 5, 15, and 30 minutes at 10, 20, and 30°C. Bactericidal activity was neutralized with 0.5% sodium thiosulfate. Mean viable colony forming units (CFUs) was determined after triplicate plating on Luria-bertani agar and 24 hours of incubation at 37°C. Effective bactericidal activity was defined as a 5-log reduction. Results Of the 200,000 E. coli plated, no CFUs were observed after exposure to the 1:100 dilution. After 5 minutes of contact time with the 1:1,000 dilution, at 10°C CFUs were too numerous to count (TNTC), at 20°C the mean CFU count was 92 (standard error ±11), and at 30°C the mean CFU count was 25 (standard error ±8). No CFUs were observed after 15 minutes of exposure to the 1:1,000 dilution across experimental temperatures. The 1:10,000 dilution always yielded CFU growth that was TNTC. Conclusions The lowest disinfecting concentration of 10% PVI was the 1:1,000 dilution at 15 minutes of contact time. This supports the use of PVI for water disinfection against E. coli, the organism most commonly responsible for traveler's diarrhea. Further studies may assess its effectiveness against more virulent water borne pathogens.