tbuckley/cabot-search huggingface dataset:
Association of Parkinson’s Disease and Its Subtypes with Agricultural Pesticide Exposures in Men: A Case–Control Study in France
Authors: Frédéric Moisan, Johan Spinosi, Laurène Delabre, Véronique Gourlet, Jean-Louis Mazurie, Isabelle Bénatru, Marcel Goldberg, Marc G. Weisskopf, Ellen Imbernon, Christophe Tzourio, Alexis Elbaz
Journal: Environmental Health Perspectives (2015)

Pesticides have been associated with Parkinson's disease (PD), but there are few data on important exposure characteristics such as dose-effect relations. It is unknown whether associations depend on clinical PD subtypes.We examined quantitative aspects of occupational pesticide exposure associated with PD and investigated whether associations were similar across PD subtypes.As part of a French population-based case-control study including men enrolled in the health insurance plan for farmers and agricultural workers, cases with clinically confirmed PD were identified through antiparkinsonian drug claims. Two controls were matched to each case. Using a comprehensive occupational questionnaire, we computed indicators for different dimensions of exposure (duration, cumulative exposure, intensity). We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) among exposed male farmers (133 cases, 298 controls). We examined the relation between pesticides and PD subtypes (tremor dominant/non-tremor dominant) using polytomous logistic regression.There appeared to be a stronger association with intensity than duration of pesticide exposure based on separate models, as well as a synergistic interaction between duration and intensity (p-interaction = 0.04). High-intensity exposure to insecticides was positively associated with PD among those with low-intensity exposure to fungicides and vice versa, suggesting independent effects. Pesticide exposure in farms that specialized in vineyards was associated with PD (OR = 2.56; 95% CI: 1.31, 4.98). The association with intensity of pesticide use was stronger, although not significantly (p-heterogeneity = 0.60), for tremor-dominant (p-trend < 0.01) than for non-tremor-dominant PD (p-trend = 0.24).This study helps to better characterize different aspects of pesticide exposure associated with PD, and shows a significant association of pesticides with tremor-dominant PD in men, the most typical PD presentation.Moisan F, Spinosi J, Delabre L, Gourlet V, Mazurie JL, Bénatru I, Goldberg M, Weisskopf MG, Imbernon E, Tzourio C, Elbaz A. 2015. Association of Parkinson's disease and its subtypes with agricultural pesticide exposures in men: a case-control study in France. Environ Health Perspect 123:1123-1129; http://dx.doi.org/10.1289/ehp.1307970.
Preinfarction angina as a major predictor of left ventricular function and long-term prognosis after a first Q wave myocardial infarction
Authors: Toshihisa Anzai, Tsutomu Yoshikawa, Yasushi Asakura, Sumihisa Abe, Makoto Akaishi, Hideo Mitamura, Shunnosuke Handa, Satoshi Ogawa
Journal: Journal of the American College of Cardiology (1995)
780-6 Effect of Long Term Prostacyclin (PGI2) on Exercise in Patients with Primary Pulmonary Hypertension (PPH) Who Have Deteriorated on Maximal Conventional Therapy
Authors: David F. Wax, Robert Garofano, Welton M. Gersony, Robyn J. Barst
Journal: Journal of the American College of Cardiology (1995)
983. Inhibition of Hepatitis C Virus Replication by In Vitro Selected Specific RNA Aptamers
Authors: Jung-Hye Kim, Nam Yeon Kim, Seong-Wook Lee
Journal: Molecular Therapy (2005)

Top of pageAbstract
Hepatitis C virus (HCV) is the main etiological agent of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the HCV infection causes worldwide health problem, efficient and specific antiviral therapy has not yet been developed. Thus, development of more specific and effective therapeutics against HCV is warranted. The RNA dependent RNA polymerase (NS5B) of HCV plays a central role in the viral replication. Therefore, NS5B is a good target for anti-HCV agents. Characteristics of RNAs which can adopt complex structures to bind target proteins with high affinities and encode amplificable genetic information make RNA a potentially very useful diagnostic and/or therapeutic lead compounds. Such short RNA ligands, termed RNA aptamers, have been identified from a random RNA library to bind several proteins with high affinity and specificity using in vitro selection techniques, called systemic evolution of ligands by exponential enrichment (SELEX). In the present study, we isolated RNA aptamers to NS5B from a combinatorial RNA library using SELEX techniques and analyzed the biochemical and biological functions of the RNA aptamers. The RNA aptamers were found to specifically and avidly bind NS5B with an apparent Kd of 1.3|[sim]|4 nM. Through enzymatic probing and footprinting analysis, critical regions of the RNAs for NS5B binding have been identified. Moreover, in vitro RNA synthesis by NS5B was significantly inhibited by the RNA aptamers. Interestingly, the RNA aptamers can be utilized as substrates for de-novo RNA synthesis by NS5B. Specific interaction between the RNAs and NS5B was confirmed by Maldi-Tof analysis of the aptamer-bound proteins in liver cells with HCV replicon. Importantly, the replication of HCV replicon in liver cells was efficiently inhibited by cytoplasmic expression of the RNA aptamers, but not by nuclear expression of the RNAs. In addition, we showed that these aptamers could function as decoys in HCV replicon cells, explaining the mechanism underlying inhibition phenomena of HCV replicon replication observed in cells by the specific RNA aptamers against HCV NS5B. These results suggest that the RNA aptamers could be useful not only as therapeutic and diagnostic agents of HCV infection but also as a powerful tool for the study of HCV replication mechanism.
Pharmacologic identification of the lower esophageal sphincter
Authors: James Christensen
Journal: Journal of Clinical Investigation (1970)

The distal 2/3 of the opossum esophagus contains only smooth muscle. Manometry shows that the most distal 1-2 cm is the lower esophageal sphincter. We used a variety of agonists to seek differences between circular muscle from the sphincteric segment and more rostral levels. Isometric contractions of strips from the distal 6 cm were recorded in vitro in response to acetylcholine, carbachol, methacholine, nicotine. DMPP, norepinephrine, norepinephrine with propranolol, barium, atropine, and potassium. Significant differences in threshold concentration occurred for all drugs except barium, atropine, and potassium, the more distal strips being more sensitive. The gradient of threshold was much steeper for norepinephrine than for the other drugs. Maximal responses did not differ among levels for the choline esters or ganglionic stimulants, but showed proximal diminution for norepinephrine. These differences in threshold concentration could represent differences in distribution density of drug receptor sites, differences in affinity of receptors for the agonists, differences in rates of uptake of agonists, or differences in rates of enzymatic hydrolysis; or they may have no common basis. The sphincter is defined, at least in part, in the esophageal wall rather than in the central nervous system. The greater magnitude of the difference in sensitivity to norepinephrine than for the other agents suggests that the adrenergic innervation is important in defining the lower esophageal sphincter.
Effect of altitude on physiological performance: a statistical analysis using results of international football games
Authors: Patrick E McSharry
Journal: BMJ (2007)

To assess the effect of altitude on match results and physiological performance of a large and diverse population of professional athletes.Statistical analysis of international football (soccer) scores and results.FIFA extensive database of 1460 football matches in 10 countries spanning over 100 years.Altitude had a significant (P<0.001) negative impact on physiological performance as revealed through the overall underperformance of low altitude teams when playing against high altitude teams in South America. High altitude teams score more and concede fewer goals with increasing altitude difference. Each additional 1000 m of altitude difference increases the goal difference by about half of a goal. The probability of the home team winning for two teams from the same altitude is 0.537, whereas this rises to 0.825 for a home team with an altitude difference of 3695 m (such as Bolivia v Brazil) and falls to 0.213 when the altitude difference is -3695 m (such as Brazil v Bolivia).Altitude provides a significant advantage for high altitude teams when playing international football games at both low and high altitudes. Lowland teams are unable to acclimatise to high altitude, reducing physiological performance. As physiological performance does not protect against the effect of altitude, better predictors of individual susceptibility to altitude illness would facilitate team selection.
Neurological disorders and adult coeliac disease
Authors: J. S. Morris, A. B. Ajdukiewicz, A. E. Read
Journal: Gut (1970)

An investigation into the incidence of neurological disorder in 30 patients with adult coeliac disease has shown that three patients had severe depression, two had epileptiform convulsions, and one patient only had signs of involvement of the peripheral nervous system. Motor nerve conduction velocity was low in only one patient. When the nerve conduction velocities of the group on a gluten-free diet were compared with the group who were not on a gluten-free diet, there was no statistically significant difference. Similarly, nerve conduction velocities in patients with a low serum pyridoxal level were not significantly different from those with normal serum pyridoxal levels. Measurements of the serum level of pyridoxal in 30 patients confirmed that pyridoxine deficiency occurs in adult coeliac disease and that the restriction of gluten from the diet appeared to affect pyridoxal levels favourably.
The Value of Medical Spending in the United States, 1960–2000
Authors: David M. Cutler, Allison B. Rosen, Sandeep Vijan
Journal: New England Journal of Medicine (2006)

The increased use of medical therapies has led to increased medical costs. To provide insight into the value of this increased spending, we compared gains in life expectancy with the increased costs of care from 1960 through 2000.We estimated life expectancy in 1960, 1970, 1980, 1990, and 2000 for four age groups. To control for the influence of nonmedical factors on survival, we assumed in our base-case analysis that 50 percent of the gains were due to medical care. We compared the adjusted increases in life expectancy with the lifetime cost of medical care in the same years.From 1960 through 2000, the life expectancy for newborns increased by 6.97 years, lifetime medical spending adjusted for inflation increased by approximately 69,000 dollars, and the cost per year of life gained was 19,900 dollars. The cost increased from 7,400 dollars per year of life gained in the 1970s to 36,300 dollars in the 1990s. The average cost per year of life gained in 1960-2000 was approximately 31,600 dollars at 15 years of age, 53,700 dollars at 45 years of age, and 84,700 dollars at 65 years of age. At 65 years of age, costs rose more rapidly than did life expectancy: the cost per year of life gained was 121,000 dollars between 1980 and 1990 and 145,000 dollars between 1990 and 2000.On average, the increases in medical spending since 1960 have provided reasonable value. However, the spending increases in medical care for the elderly since 1980 are associated with a high cost per year of life gained. The national focus on the rise in medical spending should be balanced by attention to the health benefits of this increased spending.
Abstract P3-15-02: A prospective, open label, non-comparative trial to determine the incidence of chemotherapy-induced nausea and vomiting associated with the docetaxel-cyclophosphamide regimen in early breast cancer patients. Results from the GEICAM 2009-02 study
Authors: V Carañana, M Ramos, E Damau, JA García-Saenz, X González, L Murillo, L Calvo, S Morales, A González-Farré, LA Fernández-Morales, E Carrasco, MI Casas, MdM Angulo, MC Cámara, AI García, A Llombart, C Jara
Journal: Cancer Research (2013)

Abstract Background: Docetaxel-Cyclophosphamide (TC) has become a common chemotherapy regimen for moderate-high risk Early Breast Cancer (EBC) patients. The incidence of chemotherapy induced nausea and vomiting (CINV) with TC together with an adequate standard anti-emetic therapy with 5-HT3 antagonist and corticosteroids are unknown. This study investigates the incidence of emesis control (complete response), defined as no vomiting (any grade of NCI CTCAE version 4.0) and no use of rescue treatment within 120 hours after the first cycle of TC. Secondary objective evaluates the efficacy of Aprepitant in non-responding patients. Methods: EBC patients with no prior moderate-high risk CINV were included. Patients received Docetaxel 75 mg/m2 plus Cyclophosphamide 600 mg/m2 IV every three weeks. Antiemetic treatment consisted of oral Dexamethasone (D) 8 mg (at night) on day 0; oral D 8 mg x 3 (in the morning, 1 hour before chemotherapy and at night) plus 5-HT3 antagonists on day 1; and oral D 8 mg x 2 (in the morning and at night) on days 2 and 3. Non-responding patients (vomiting or need of rescue therapy in the first cycle) were offered participation in the efficacy phase (Aprepitant 125mg day 1 and 80 mg days 2 and 3 added to the standard antiemetic therapy in cycle 2). In addition to the standard NCI-CTCAE adverse event collection, a patient´s diary (from day 1 to 6) and the FLIE (Functional Living Index-Emesis questionnaire) were used. Assuming a 25% (+/- 6%) of patients resistant to standard antiemetic therapy, 212 patients were estimated. Results: From May-11 to March-13, 212 EBC patients were included. Median age was 57 years (range 34-82), 29.3% were premenopausal. Twenty-seven patients were excluded from the main analysis because of major protocol violations (25) or consent withdrawal (2). Twenty-four patients (13%; IC95%: 8.2 – 17.8) did not respond to standard antiemetics and entered the efficacy phase with Aprepitant. From these 24 patients, 14 (56%; IC95%: 36.5 – 75.5) achieved a complete response on cycle 2. No adverse events related to Aprepitant were observed. Conclusions: Proper use of standard antiemetic therapy for early breast cancer patients treated with TC provides a high control rate (87%). Among no responding patients, about half of them were rescued with Aprepitant. Identification of the non-responding patients could lead to a better antiemetic control with Aprepitant from the first cycle. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-02.
Pulmonary hypertension after lung irradiation in infancy.
Authors: P Butler, P Chahal, N M Hudson, P J Hubner
Journal: BMJ (1981)

Pulmonary hypertension after lung irradiation in infancyIrradiation of the lung may lead to several complications including pneumonitis, pulmonary fibrosis, pleural effusion, and pneumo- thorax.The development of pulmonary hypertension is less well known and was not recorded in either of two recent reviews of the complications of radiotherapy.' 2 We report a case here. Case reportA 14-year-old girl presented with an 18-month history of syncope and mild dyspnoea on effort.At the age of 7 months a neuroblastoma arising from
Cortical Folding Defects as Markers of Poor Treatment Response in First-Episode Psychosis
Authors: Lena Palaniyappan, Tiago Reis Marques, Heather Taylor, Rowena Handley, Valeria Mondelli, Stefania Bonaccorso, Annalisa Giordano, Grant McQueen, Marta DiForti, Andrew Simmons, Anthony S. David, Carmine M. Pariante, Robin M. Murray, Paola Dazzan
Journal: JAMA Psychiatry (2013)

At present, no reliable predictors exist to distinguish future responders from nonresponders to treatment during the first episode of psychosis. Among potential neuroimaging predictors of treatment response, gyrification represents an important marker of the integrity of normal cortical development that may characterize, already at illness onset, a subgroup of patients with particularly poor outcome.To determine whether patients with first-episode psychosis who do not respond to 12 weeks of antipsychotic treatment already have significant gyrification defects at illness onset.Case-control study with 12 weeks' longitudinal follow-up to determine treatment response.Secondary psychiatric services in an inner-city area (South London, England).A total of 126 subjects, including 80 patients presenting with first-episode psychosis and 46 healthy controls. Patients were scanned at the outset and received various antipsychotic medications in a naturalistic clinical setting. They were followed up for 12 weeks and classified as responders or nonresponders if they reached criteria for symptom remission, evaluated with the Psychiatric and Personal History Schedule.Patients were exposed to naturalistic antipsychotic treatment for 12 weeks following a magnetic resonance imaging scan.Cortical gyrification was assessed using local gyrification index in a vertexwise fashion across the entire cortical surface with correction for multiple testing using permutation analysis. Differences in local gyrification index were assessed between responders, nonresponders, and healthy controls. The effect of diagnosis (affective vs nonaffective psychosis) on the local gyrification index was also investigated in responders and nonresponders.Patients with first-episode psychosis showed a significant reduction in gyrification (hypogyria) across multiple brain regions compared with healthy controls. Interestingly, nonresponders showed prominent hypogyria at bilateral insular, left frontal, and right temporal regions when compared with responders (all clusters significant at P < .05). These effects were present for both affective and nonaffective psychoses.Gyrification appears to be a useful predictor of antipsychotic treatment response. Early neurodevelopmental aberrations may predict unfavorable prognosis in psychosis, irrespective of the existing diagnostic boundaries.
Adverse outcomes of underuse of beta-blockers in elderly patients
Authors: K. L. Lapane
Journal: JAMA (1997)

To the Editor.  —The article by Soumerai and colleagues 1 provides valuable evidence to support existing guidelines to prescribe β-blockers for secondary prevention of AMI. While the authors mention that barriers to prescribing β-blockers include exaggerated concerns regarding adverse effects on quality of life, they do not consider the implications of this on their findings.  As the authors acknowledge, β-blocker use is not recommended in patients with a history of depression. 2 Furthermore, depression has recently been linked to coronary heart disease morbidity and mortality. 3,4 As depressed people may be more likely to receive calcium channel blockers than β-blockers and also are more likely to have future cardiac events, confounding by depression could explain the reported association. While the authors may not be able to evaluate this adequately as the cross-linked data sets they are using may not have reliable information on depression, perhaps they could control for antidepressant use as a
Abstract 4154: Exosomal microRNAs: mediators for cell-cell communications
Authors: Ramesh Singh, Yin Yuan Mo
Journal: Cancer Research (2012)

Abstract Background: Exosomes are 30-100nm membrane vesicles of endocytic origin, mediating diverse biological functions including tumor-cell invasion, cell-cell communication and antigen presentation through transfer of proteins, mRNAs and microRNAs to neighboring or distant cells. MicroRNAs are small regulatory non-coding RNA molecules that regulate protein-coding genes. Recent evidence suggests that microRNAs can be released through ceramide-dependent secretory machinery regulated by neutral sphingomyelinase 2 (nSMase2) enzyme expressed by smpd3 gene that triggers exosome secretion. In this study, we investigated the exosome-mediated microRNA transfer among various types of cells, the regulation of exosome-mediated microRNA secretion and functional role of these exosomal microRNAs inside the recipient cell after uptake. Methods: Exosomes were isolated from culture media of cells by serial centrifugation, filtration and ultracentrifugation method. Isolated exosomes were stained with PKH26 dye and then observed for cellular uptake in different cells by confocal microscopy after counterstaining with Hoechst stain. In addition, this uptake was also shown by exosome isolated from stable 293T cell line overexpressing the pCDH-CD63-GFP fusion protein. To determine the effect of nSMase2 on exosome secretion, stable cell lines were established with smpd3 gene. Levels of microRNAs secreted in media were determined by real time PCR. To validate the function of exosomal microRNA in the recipient cells, we determined the protein level of microRNA target genes by western blot. Results: We first showed that exosomes can be transferred among different cell lines through direct uptake. We found that miR-10b is highly expressed in metastatic breast cancer MDA-MB-231 cells as compared to non-metastatic breast cells; it is actively secreted into medium. For example, nSMase2 promoted the exosome-mediated miR-10b secretion whereas ceramide inhibitor suppressed this secretion. Importantly, western blot revealed that upon uptake, miR-10b can still reduce the protein level of its target genes such as Bim, indicating its functional significance. Conclusion: We found that the exosomes secreted from cancer cells containing microRNA can be taken up by other cells and have functional role in the recipient cells suggesting the importance of exosome-mediated microRNA transfer in tumor microenvironment. Our results collectively suggest that a set of specific microRNAs may play an important role in modulating tumor microenvironment through exosomes. Thus, a better understanding of this process may aid in the development of novel therapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4154. doi:1538-7445.AM2012-4154