tbuckley/cabot-search huggingface dataset:
Obesity Is A Modifier of Autonomic Cardiac Responses to Fine Metal Particulates
Authors: Jiu-Chiuan Chen, Jennifer M. Cavallari, Peter H. Stone, David C. Christiani
Journal: Environmental Health Perspectives (2007)

BackgroundIncreasing evidence suggests that obesity may impart greater susceptibility to adverse effects of air pollution. Particulate matter, especially PM2.5 (particulate matter with aero-dynamic diameter ≤2.5 μm), is associated with increased cardiac events and reduction of heart rate variability (HRV).ObjectivesOur goal was to investigate whether particle-mediated autonomic modulation is aggravated in obese individuals.MethodsWe examined PM2.5-mediated acute effects on HRV and heart rate (HR) using 10 24-hr and 13 48-hr ambulatory electrocardiogram recordings collected from 18 boilermakers (39.5 ± 9.1 years of age) exposed to high levels of metal particulates. Average HR and 5-min HRV [SDNN: standard deviation of normal-to-normal intervals (NN); rMSSD: square-root of mean squared-differences of successive NN intervals; HF: high-frequency power 0.15–0.4 Hz] and personal PM2.5 exposures were continuously monitored. Subjects with body mass index ≥ 30 kg/m2 were classified as obese. Mixed-effect models were used for statistical analyses.ResultsHalf (50%) of the study subjects were obese. After adjustment for confounders, each 1-mg/m3 increase in 4-hr moving average PM2.5 was associated with HR increase of 5.9 bpm [95% confidence interval (CI), 4.2 to 7.7] and with 5-min HRV reduction by 6.5% (95% CI, 1.9 to 11.3%) for SDNN, 1.7% (95% CI, –4.9 to 8.4%) for rMSSD, and 8.8% (95% CI, –3.8 to 21.3%) for HF. Obese individuals had greater PM2.5-mediated HRV reductions (2- to 3-fold differences) than nonobese individuals, and had more PM2.5-mediated HR increases (9-bpm vs. 4-bpm increase in HR for each 1-mg/m3 increase in PM2.5; p < 0.001).ConclusionsOur study revealed greater autonomic cardiac responses to metal particulates in obese workers, supporting the hypothesis that obesity may impart greater susceptibility to acute cardiovascular effects of fine particles.
Impact of Androgen-Deprivation Therapy on Cognitive Function in Men With Nonmetastatic Prostate Cancer
Authors: Shabbir M.H. Alibhai, Henriette Breunis, Narhari Timilshina, Shireen Marzouk, Diane Stewart, Ian Tannock, Gary Naglie, George Tomlinson, Neil Fleshner, Murray Krahn, Padraig Warde, Sarah Duff Canning
Journal: Journal of Clinical Oncology (2010)

To evaluate the effects of androgen-deprivation therapy (ADT) on cognitive function in men with nonmetastatic prostate cancer (PC).The following three groups of men age 50 years or older and matched on age and education were enrolled: patients with PC starting continuous ADT (n = 77), patients with PC not receiving ADT (PC controls, n = 82), and healthy controls (n = 82). A battery of 14 neuropsychological tests, examining eight cognitive domains, was administered at baseline, 6 months, and 12 months. Changes in cognitive scores over time were analyzed using the following three approaches: multivariable linear regression; the proportion of participants per group with 1 standard deviation (SD) or greater declines, and the proportion of participants who declined by at least 1.5 SD on two or more tests.The mean age and education level of participants were 68.9 years (range, 50 to 87 years) and 15.4 years of education (range, 8 to 24 years), respectively. Adjusted for age and education, all three cohorts had similar cognitive scores at baseline other than in one test of working memory. In adjusted regressions, ADT use was not associated with significant changes in the domains of attention/processing speed, verbal fluency, verbal memory, visual memory, or cognitive flexibility at either 6 months (all P > .05) or 12 months (all P > .05). One test each of immediate memory (P = .029), working memory (P = .031), and visuospatial ability (P = .034) were worse among ADT users than controls at 12 months, but these findings were not confirmed using other analytic approaches.There is no consistent evidence that 12 months of ADT use has an adverse effect on cognitive function in elderly men with PC.
Risk-Adjusted Pathologic Margin Positivity Rate As a Quality Indicator in Rectal Cancer Surgery
Authors: Nader N. Massarweh, Chung-Yuan Hu, Y. Nancy You, Brian K. Bednarski, Miguel A. Rodriguez-Bigas, John M. Skibber, Scott B. Cantor, Janice N. Cormier, Barry W. Feig, George J. Chang
Journal: Journal of Clinical Oncology (2014)

Margin positivity after rectal cancer resection is associated with poorer outcomes. We previously developed an instrument for calculating hospital risk-adjusted margin positivity rate (RAMP) that allows identification of performance-based outliers and may represent a rectal cancer surgery quality metric.This was an observational cohort study of patients with rectal cancer within the National Cancer Data Base (2003 to 2005). Hospital performance was categorized as low outlier (better than expected), high outlier (worse than expected), or non-RAMP outlier using standard observed-to-expected methodology. The association between outlier status and overall risk of death at 5 years was evaluated using Cox shared frailty modeling.Among 32,354 patients with cancer (mean age, 63.8 +/-13.2 years; 56.7% male; 87.3% white) treated at 1,349 hospitals (4.9% high outlier, 0.7% low outlier), 5.6% of patients were treated at high outliers and 3.0% were treated at low outliers. Various structural (academic status and volume), process (pathologic nodal evaluation and neoadjuvant radiation therapy use), and outcome (sphincter preservation, readmission, and 30-day postoperative mortality) measures were significantly associated with outlier status. Five-year overall survival was better at low outliers (79.9%) compared with high outliers (64.9%) and nonoutliers (68.9%; log-rank test, P < .001). Risk of death was lower at low outliers compared with high outliers (hazard ratio [HR], 0.61; 95% CI, 0.50 to 0.75) and nonoutliers (HR, 0.69; 95% CI, 0.57 to 0.83). Risk of death was higher at high outliers compared with nonoutliers (HR, 1.12; 95% CI, 1.03 to 1.23).Hospital RAMP outlier status is a rectal cancer surgery composite metric that reliably captures hospital quality across all levels of care and could be integrated into existing quality improvement initiatives for hospital performance.
Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.
Authors: U McKeever, S Khandekar, J Newcomb, J Naylor, P Gregory, P Brauer, M Jesson, B Bettencourt, E Burke, A Alderson, J Banerji, K Haskins, B Jones
Journal: The Journal of Experimental Medicine (1996)

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.
Genetic Abnormalities Associated with Chemoradiation Resistance of Head and Neck Squamous Cell Carcinoma
Authors: Guido B. van den Broek, Volkert B. Wreesmann, Michiel W.M. van den Brekel, Coen R.N. Rasch, Alfons J.M. Balm, Pulivarthi H. Rao
Journal: Clinical Cancer Research (2007)

To identify reliable predictors of chemoradiation resistance of advanced head and neck squamous cell carcinoma (HNSCC).We did a matched-pair analysis of 20 chemoradiation-resistant and 20 sensitive HNSCCs, identified among a series of 104 consecutively treated cases. We compared the global DNA copy number profiles derived from comparative genomic hybridization analysis of both groups to identify genetic markers associated with chemoradiation resistance.Although sensitive and resistant case groups were characterized by a similar total number of genetic aberrations, high-level amplifications were more frequent in resistant tumors. Resistant tumors were characterized by a different profile of genetic changes. Gains of 3q11-q13, 3q21-q26.1, and 6q22-q27 and losses of 3p11-pter and 4p11-pter were significantly associated with chemoradiation resistance. High-level amplifications unique to resistant cases involved the chromosomal regions 1p32, 3q24, 7p11.1, 7p11.2-12, 8p11.1, 8p11.1-12, 12q15, 13q21, 15q12, 18p11.3, and 18q11.Sensitive and resistant HNSCCs are characterized by divergent genomic profiles. These profiles may be valuable as predictive markers of treatment failure.
The investigation of overactive bladder symptoms in patients with obstructive sleep apnea syndrome
Authors: Önder Öztürk, Taylan Oskay, Tahsin Çapkin, Alim Kosar, Ahmet Akkaya, Osman Çelik
Journal: European Respiratory Journal (2013)

Aim: In this study, the symptoms of overactive bladder (OAB) were investigated in patients with obstructive sleep apnea syndrome (OSAS).  Material and methods: The patients having snoring,witnessed apnea, daytime sleepiness complaints and diagnosed as OSAS [apnea-hypopnea index >=5] by polysomnography (PSG) were included to the study. The patients were examined by urologist and filled a questionnaire which consisted of 4 questions. The demographic properties, PSG data and OAB results were recorded. The patients were divided into two groups: Group 1 (AHI =5)  Results: Sixty four of 77 patients answered the qustionnaire. Twenty patients were excluded from the study because of insufficient data. So the data of 44 patients were evaluated. The patients who had sleep disorderes. Due to PSG, 7 (M/W:4/3) patients had AHI =5 (34.48±4.75 e/hr, VKI 30.78±1.01 kg/m2).The OAB score of groups were respectively; 2.86±0.55 and 3.73 ± 0.49 (p>0.05). There was a positive correlation between OAB score and AHI (r=0.341,p=0.039). Although one patient had pollakiuria, Grup2 had 11 pollakiuria. There were 19 urgency incontinence and 10 missed urine in Group 2. The urgency incontinence (n=12) were mostly seen symptoms in patients with AHI>=30. The pollakiuria (n=7), nocturia (>=3) (n=9) and urgency incontinence (n=13) were seen more in patients with ODI>=30.  Conclusion: There was a relationship between OSAS and OAB symptoms and OAB symptoms increase with the severity of the disease. Thus, the patients should be questioned for sleep diorders during the diagnosis of OAB.
Phase II trial of irinotecan and thalidomide in adults with recurrent glioblastoma multiforme
Authors: Vinay K. Puduvalli, Pierre Giglio, Morris D. Groves, Kenneth R. Hess, Mark R. Gilbert, Srikanth Mahankali, Edward F. Jackson, Victor A. Levin, Charles A. Conrad, Sigmund H. Hsu, Howard Colman, John F. de Groot, MeLesa G. Ritterhouse, Sandra E. Ictech, W. K. Alfred Yung
Journal: Neuro-Oncology (2008)

This phase II study aimed at determining the efficacy and safety of irinotecan combined with thalidomide in adults with recurrent glioblastoma multiforme (GBM) not taking enzyme-inducing anticonvulsants (EIACs). Adult patients (> or =18 years) with recurrent GBM with up to three relapses following surgery and radiation therapy were eligible for this trial. The primary end point was rate of progression-free survival at 6 months (PFS-6); secondary end points were response rate, overall survival, and toxicity. Patients were treated in 6-week cycles with 125 mg/m(2) irinotecan weekly for 4 weeks followed by 2 weeks off treatment and 100 mg of thalidomide daily increased as tolerated to 400 mg/day. Of 32 evaluable patients, 8 (25%) were alive and progression free at 6 months. The median PFS was 13 weeks. One patient experienced a complete response, one a partial response, and 19 stable disease. Median overall survival time from entry into the study was 36 weeks, and the 1-year survival rate was 34%. Adverse events (grade 3 or 4) included diarrhea, abdominal cramps, lymphopenia, neutropenia, and fatigue. Two of the four deaths that occurred were possibly due to treatment-related toxicity. The combination of irinotecan, a cytotoxic agent, and thalidomide, an antiangiogenic agent, shows promising activity against recurrent GBM in patients not receiving EIACs and warrants further study. The results also provide support for similar strategies using combination therapies with newer targeted antiangiogenic agents to generate effective therapies against malignant gliomas.
Reduced Expression of Metastasis Suppressor RhoGDI2 Is Associated with Decreased Survival for Patients with Bladder Cancer
Authors: Dan Theodorescu, L. M. Sapinoso, M. R. Conaway, G. Oxford, G. M. Hampton, H. F. Frierson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: RhoGDI2 was recently shown to be a metastasis suppressor gene in models of bladder cancer. We sought to further understand its importance in human cancer by determining the level of its expression and the distribution of its encoded protein in normal human tissues and cell lines and to evaluate whether its protein expression is a determinant of human bladder cancer progression. Experimental Design: RhoGDI2 mRNA and protein expression was evaluated in cell lines and human tissues using Affymetrix and tissue microarrays, respectively. Tissue microarrays represented most human normal adult tissues and material from 51 patients that had undergone radical cystectomy for bladder cancer. In these 51 patients, the χ2 test was used to test for associations between RhoGDI2 and stage, grade of urothelial carcinoma, histological type, and disease-specific survival status. Cox proportional hazards regression analyses were used to estimate the effect of RhoGDI2 expression level on time to development of metastatic disease and disease-specific survival time, adjusting for grade, stage, and histological type. Results: In normal tissues, there was strong RhoGDI2 protein expression in WBCs, endothelial cells, and transitional epithelium. RhoGDI2 mRNA expression was inversely related to the invasive and metastatic phenotype in human bladder cancer cell lines. In patients with bladder cancer, univariate analysis indicated that reduced tumor RhoGDI2 protein expression was associated with a lower actuarial 5-year disease-free and disease-specific survival (P = 0.01). In addition, patients with tumors that had low or absent RhoGDI2 had a shorter time to disease-specific death (P ≤ 0.01). When tumor grade, stage, histological type, and RhoGDI2 staining level were examined using multivariate analysis, RhoGDI2 expression was found to be an independent predictive factor for disease-specific death (P = 0.03). Conclusions: These results suggest that RhoGDI2 is an independent predictor of prognosis for patients with bladder cancer and provide clinical evidence in support of its involvement in cancer metastasis.
Constructing an understanding of mind: The development of children's social understanding within social interaction
Authors: Jeremy I. M. Carpendale, Charlie Lewis
Journal: Behavioral and Brain Sciences (2004)

Theories of children's developing understanding of mind tend to emphasize either individualistic processes of theory formation, maturation, or introspection, or the process of enculturation. However, such theories must be able to account for the accumulating evidence of the role of social interaction in the development of social understanding. We propose an alternative account, according to which the development of children's social understanding occurs within triadic interaction involving the child's experience of the world as well as communicative interaction with others about their experience and beliefs (Chapman 1991; 1999). It is through such triadic interaction that children gradually construct knowledge of the world as well as knowledge of other people. We contend that the extent and nature of the social interaction children experience will influence the development of children's social understanding. Increased opportunity to engage in cooperative social interaction and exposure to talk about mental states should facilitate the development of social understanding. We review evidence suggesting that children's understanding of mind develops gradually in the context of social interaction. Therefore, we need a theory of development in this area that accords a fundamental role to social interaction, yet does not assume that children simply adopt socially available knowledge but rather that children construct an understanding of mind within social interaction.
Adverse Events Associated With Smallpox Vaccination in the United States, January-October 2003
Authors: Christine G Casey, John K Iskander, Martha H Roper, Eric E Mast, Xiao-Jun Wen, Thomas J Török, Louisa E Chapman, David L Swerdlow, Juliette Morgan, James D Heffelfinger, Charles Vitek, Susan E Reef, La Mar Hasbrouck, Inger Damon, Linda Neff, Claudia Vellozzi, Mary McCauley, Raymond A Strikas, Gina Mootrey
Journal: JAMA (2005)

On January 24, 2003, the US Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a bioterrorism event.To describe results from the comprehensive DHHS smallpox vaccine safety monitoring and response system.Descriptive study of adverse event reports from the DHHS smallpox vaccine safety monitoring and response system received between January 24 and October 31, 2003, through the Vaccine Adverse Event Reporting System (VAERS) and the Centers for Disease Control and Prevention. A total of 37,901 volunteers in 55 jurisdictions received at least 1 dose of smallpox vaccine.Number of vaccinations administered and description of adverse events and reporting rates.A total of 38,885 smallpox vaccinations were administered, with a take rate of 92%. VAERS received 822 reports of adverse events following smallpox vaccination (overall reporting rate, 217 per 10,000 vaccinees). A total of 590 adverse events (72%) were reported within 14 days of vaccination. Nonserious adverse events (n = 722) included multiple signs and symptoms of mild and self-limited local reactions. One hundred adverse events (12%) were designated as serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the serious adverse events, 21 cases were classified as myocarditis and/or pericarditis and 10 as ischemic cardiac events that were not anticipated based on historical data. Two cases of generalized vaccinia and 1 case of postvaccinial encephalitis were detected. No preventable life-threatening adverse reactions, contact transmissions, or adverse reactions that required treatment with vaccinia immune globulin were identified. Serious adverse events were more common among older revaccinees than younger first-time vaccinees.Rigorous smallpox vaccine safety screening, educational programs, and older vaccinees may have contributed to low rates of preventable life-threatening adverse reactions. Other rare, clinically significant, or unexpected cardiac adverse events were detected by timely review of VAERS data and intensive clinical case investigation.
Endogenous endothelins and nitric oxide in hypoxic pulmonary vasoconstriction
Authors: I. Hubloue, D. Biarent, S. Abdel Kafi, G. Bejjani, F. Kerbaul, R. Naeije, M. Leeman
Journal: European Respiratory Journal (2003)

The effects of endothelin receptor blockade on the pulmonary circulation have been reported variably, possibly in relation to a more or less important associated release of endogenous nitric oxide (NO). The aim of this study was to test whether endothelin antagonism would inhibit hypoxic pulmonary vasoconstriction, and if it would not, then would it do so after NO synthase inhibition. Hypoxic pulmonary vasoconstriction (HPV) was evaluated in anesthetised dogs by the increase in the mean pulmonary artery pressure (<i>P</i><sub>pa</sub>) minus occluded <i>P</i><sub>pa</sub> (<i>P</i><sub>pao</sub>) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Bosentan, an endothelin A and B receptor antagonist, did not affect baseline <i>P</i><sub>pa</sub>, <i>P</i><sub>pao</sub> or systemic arterial pressure (<i>P</i><sub>sa</sub>) and did not alter HPV (n=8). The NO synthase inhibitor N<sup>G</sup>­nitro‐l‐arginine (l‐NA) did not affect baseline <i>P</i><sub>pa</sub> and <i>P</i><sub>pao</sub>, but increased <i>P</i><sub>sa</sub> and enhanced HPV (n=12). The addition of bosentan in these dogs did not affect baseline <i>P</i><sub>pa</sub> or <i>P</i><sub>pao</sub>, but decreased <i>P</i><sub>sa</sub> and inhibited HPV. Exhaled NO was decreased by l‐NA and by bosentan and abolished by l‐NA+bosentan (n=9). The authors conclude that endogenous nitric oxide is released by, and opposes the vasoconstricting effects of, endothelins <i>in vivo</i>, reducing systemic blood pressure and limiting hypoxic pulmonary vasoconstriction.
Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms
Authors: Clare M. Gladding, Stephen M. Fitzjohn, Elek Molnár
Journal: Pharmacological Reviews (2009)

The ability to modify synaptic transmission between neurons is a fundamental process of the nervous system that is involved in development, learning, and disease. Thus, synaptic plasticity is the ability to bidirectionally modify transmission, where long-term potentiation and long-term depression (LTD) represent the best characterized forms of plasticity. In the hippocampus, two main forms of LTD coexist that are mediated by activation of either <i>N</i>-methyl-d-aspartic acid receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). Compared with NMDAR-LTD, mGluR-LTD is less well understood, but recent advances have started to delineate the underlying mechanisms. mGluR-LTD at CA3:CA1 synapses in the hippocampus can be induced either by synaptic stimulation or by bath application of the group I selective agonist (<i>R</i>,<i>S</i>)-3,5-dihydroxyphenylglycine. Multiple signaling mechanisms have been implicated in mGluR-LTD, illustrating the complexity of this form of plasticity. This review provides an overview of recent studies investigating the molecular mechanisms underlying hippocampal mGluR-LTD. It highlights the role of key molecular components and signaling pathways that are involved in the induction and expression of mGluR-LTD and considers how the different signaling pathways may work together to elicit a persistent reduction in synaptic transmission.