tbuckley/cabot-search huggingface dataset:
Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis
Authors: A E Holland
Journal: Thorax (2003)

Background: Chest physiotherapy is essential to the management of cystic fibrosis (CF). However, respiratory muscle fatigue and oxygen desaturation during treatment have been reported. The aim of this study was to determine whether non-invasive ventilation (NIV) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF. Methods: Twenty six patients of mean (SD) age 27 (6) years and forced expiratory volume in 1 second (FEV1) 34 (12)% predicted completed a randomised crossover trial comparing standard treatment (active cycle of breathing technique, ACBT) with ACBT + NIV. Respiratory muscle strength (PImax, PEmax), spirometric parameters, and dyspnoea were measured before and after treatment. Pulse oximetry (Spo2) was recorded during treatment. Sputum production during treatment and 4 and 24 hours after treatment was evaluated. Results: There was a significant reduction in PImax following standard treatment that was correlated with baseline PImax ( r =0.73, p<0.001). PImax was maintained following NIV (mean difference from standard treatment 9.04 cm H2O, 95% confidence interval (CI) 4.25 to 13.83 cm H2O, p=0.006). A significant increase in PEmax was observed following the NIV session (8.04 cm H2O, 95% CI 0.61 to 15.46 cm H2O, p=0.02). The proportion of treatment time with Spo2 ⩽90% was correlated with FEV1 ( r =−0.65, p<0.001). NIV improved mean Spo2 (p<0.001) and reduced dyspnoea (p=0.02). There were no differences in FEV1, forced vital capacity (FVC) or sputum weight, but FEF25–75 increased following NIV (p=0.006). Conclusion: Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF. Addition of NIV improves inspiratory muscle function, oxygen saturation and small airway function and reduces dyspnoea.
The Complex Evolutionary History of Gorillas: Insights from Genomic Data
Authors: O Thalmann, A Fischer, F Lankester, S Paabo, L Vigilant
Journal: Molecular Biology and Evolution (2006)

Relatively little is known about the evolutionary and demographic histories of gorillas, one of our closest living relatives. In this study, we used samples from both western (Gorilla gorilla) and eastern (Gorilla beringei) gorillas to infer the timing of the split between these geographically disjunct populations and to elaborate the demographic history of gorillas. Here we present DNA sequences from 16 noncoding autosomal loci from 15 western gorillas and 3 eastern gorillas, including 2 noninvasively sampled free-ranging individuals. We find that the genetic diversity of gorillas is similar to that of chimpanzees but almost twice as high as that of bonobos and humans. A significantly positive Fu & Li's D was observed for western gorillas, suggesting a complex demographic history with a constant, long-term population size and ancestral population structure. Among different population-split scenarios, our data suggest a complex history of western and eastern gorillas including an initial population split at around 0.9–1.6 MYA and subsequent, primarily male-mediated gene flow until approximately 80,000–200,000 years ago. Furthermore, simulations revealed that more gene flow took place from eastern to western gorilla populations than vice versa.
Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease
Authors: Mantel, Nathan, Haenszel, William
Journal: JNCI Journal of the National Cancer Institute (1959)

The role and limitations of retrospective investigations of factors possibly associated with the occurrence of a disease are discussed and their relationship to forward-type studies emphasized. Examples of situations in which misleading associations could arise through the use of inappropriate control groups are presented. The possibility of misleading associations may be minimized by controlling or matching on factors which could produce such associations; the statistical analysis will then be modified. Statistical methodology is presented for analyzing retrospective study data, including chi-square measures of statistical significance of the observed association between the disease and the factor under study, and measures for interpreting the association in terms of an increased relative risk of disease. An extension of the chi-square test to the situation where data are subclassified by factors controlled in the analysis is given. A summary relative risk formula, R, is presented and discussed in connection with the problem of weighting the individual subcategory relative risks according to their importance or their precision. Alternative relative-risk formulas, R1, R2, R3, and R4, which require the calculation of subcategory-adjusted proportions of the study factor among diseased persons and controls for the computation of relative risks, are discussed. While these latter formulas may be useful in many instances, they may be biased or inconsistent and are not, in fact, averages of the relative risks observed in the separate subcategories. Only the relative-risk formula, R, of those presented, can be viewed as such an average. The relationship of the matched-sample method to the sub-classification approach is indicated. The statistical methodology presented is illustrated with examples from a study of women with epidermoid and undifferentiated pulmonary carcinoma.
The effects of sleeping position on the ventilatory response to hypercarbia
Authors: Thomas Rossor, Kamal Ali, Rebecca Trenear, Simon Hannam, Gerrard Rafferty, Anne Greenough
Journal: European Respiratory Journal (2014)

Background  Prone sleeping is an established risk factor for Sudden Infant Death Syndrome (SIDS), however the mechanism by which this contributes to vulnerability remains unclear.  Aims  To determine whether prone sleeping impairs the ventilatory response to hypercarbia in newborn infants.  Methods  Infants born at 36 weeks post-menstrual age or greater were recruited from the postnatal ward. An open circuit, consisting of a non-return valve, capnograph, and pneumotachograph, supplied gas at 4 litres/minute to a nasal mask. In both the prone and supine position baseline ventilation was measured for five minutes with the infant breathing air. The ventilatory response to either 2% or 4% carbon dioxide (CO 2 ) enriched air was then measured for five minutes. Following five minutes recovery the infants was exposed to the alternative CO 2  level, the order of gas exposure being randomised. Mean minute volume was calculated for the final minute of exposure at each gas level, and CO 2  sensitivity calculated as the gradient of the line of best fit. The time constant, defined as the time taken to achieve 63% of the maximal response to 4% CO 2  was also calculated.  Results  Thirty-one infants infants (median gestational age 39 weeks, range 36-42 weeks) were studied. There was no significant difference in the CO 2  sensitivity between positions. The time constant of the response to CO 2  was significantly longer in the prone (median 70 seconds, range 5-233 seconds) compared to the supine position (median 34 seconds, range 8-173 seconds) (p=0.031).  Conclusion  Our results suggest that a damped ventilatory response to hypercarbia may contribute to vulnerability to SIDS of infants sleeping in the prone position.
Microtubule Acetylation Through HDAC6 Inhibition Results in Increased Transfection Efficiency
Authors: Erin E Vaughan, R Christopher Geiger, Aaron M Miller, Phoebe L Loh-Marley, Takayoshi Suzuki, Naoki Miyata, David A Dean
Journal: Molecular Therapy (2008)

The success of viral and nonviral gene delivery relies on the ability of DNA-based vectors to traverse the cytoplasm and reach the nucleus. We, as well as other researchers, have shown that plasmids utilize the microtubule network and its associated motor proteins to traffic toward the nucleus. While disruption of microtubules with nocodazole was shown to greatly inhibit cytoplasmic plasmid trafficking, it did not abolish it. It has been demonstrated that a pool of stabilized post-translationally acetylated microtubules exists in cells, and that this acetylation may play a role in protein trafficking. In order to determine whether this modification could account for the residual DNA trafficking in nocodazole-treated cells, we inhibited or knocked down the levels of the tubulin deacetylase, histone deacetylase 6 (HDAC6), thereby generating higher levels of acetylated microtubules. Electroporation of plasmids into cells with inhibited or silenced HDAC6 resulted in increased gene transfer. This increased transfection efficiency was not because of increased transcriptional activity, but rather, because of increased cytoplasmic trafficking. When plasmids were cytoplasmically microinjected into HDAC6-deficient cells, they entered the nucleus within 5 minutes of injection, almost 10 times faster than in wild-type cells. Taken together, these results suggest that modulation of HDAC6 and the microtubule network can increase the efficiency of gene transfer.
The effect of social deprivation on clinical outcomes and the use of treatments in the UK cystic fibrosis population: a longitudinal study
Authors: David C Taylor-Robinson, Rosalind L Smyth, Peter J Diggle, Margaret Whitehead
Journal: The Lancet Respiratory Medicine (2013)

Poorer socioeconomic circumstances have been linked with worse outcomes in cystic fibrosis. We assessed whether a relation exists between social deprivation and individual's clinical and health-care outcomes.
Transactivation of the epidermal growth factor receptor by cag+ Helicobacter pylori induces upregulation of the early growth response gene Egr-1 in gastric epithelial cells
Authors: S Keates
Journal: Gut (2005)

Helicobacter pylori, in particular cytotoxin associated gene (cag)+ strains, have been shown to enhance gastric epithelial cell proliferation in vivo, an effect that likely contributes to gastric carcinogenesis. Early growth response gene 1 (Egr-1) is a crucial regulator of cell growth, differentiation, and survival, which is known to play a role in carcinogenesis and cancer progression. The aims of this study were to: (1) examine whether H pylori could upregulate Egr-1 in gastric epithelial cell lines; (2) determine whether there was a differential response to infection with different strains; (3) examine the role of the cag pathogenicity island in this process; and (4) elucidate the molecular mechanisms leading to Egr-1 upregulation.We found that infection of AGS cells with cag+H pylori resulted in a rapid (1-2 hours) but transient increase in Egr-1 mRNA and protein levels whereas coculture with cag- isolates did not elicit this response. Furthermore, two independent cagE- isogenic mutants of H pylori also demonstrated impaired ability to upregulate Egr-1. Upregulation of Egr-1 protein was inhibited by the extracellular regulated kinase (ERK)1/2 inhibitor PD98059 and overexpression of dominant negative MEK1 downregulated Egr-1 luciferase reporter gene activity. Treatment of AGS cells with the epidermal growth factor receptor (EGFR) kinase inhibitors PD153035 and AG1478 resulted in a reduction in H pylori mediated Egr-1 upregulation, demonstrating that EGFR transactivation plays a role in this early cellular process.Our findings show that cag+H pylori cause rapid induction of Egr-1 in gastric epithelial cells which may contribute to H pylori mediated pathogenesis.
Industrial sources of benzene exposure?
Authors: D D Rosebrook, G H Worm
Journal: Environmental Health Perspectives (1993)

LetterOpen AccessIndustrial sources of benzene exposure?is a letter which has replyCigarettes: Point Source for Benzene Exposure? D D Rosebrook and G H Worm D D Rosebrook and G H Worm Published:22 April 1993https://doi.org/10.1289/ehp.9310113AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit "Industrial sources of benzene exposure?." Environmental Health Perspectives, 101(1), pp. 13–16FiguresReferencesRelatedDetailsRelated articlesCigarettes: Point Source for Benzene Exposure?1 April 1993Environmental Health Perspectives Vol. 101, No. 1 April 1993Metrics About Article Metrics Publication History Originally published1 April 1993Published in print22 April 1993 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
Increased Arterial Carboxyhemoglobin Concentrations in Chronic Obstructive Pulmonary Disease
Authors: Hiroyasu Yasuda, Mutsuo Yamaya, Katsutoshi Nakayama, Satoru Ebihara, Takahiko Sasaki, Shoji Okinaga, Daisuke Inoue, Masanori Asada, Miyako Nemoto, Hidetada Sasaki
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases.To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking.We measured arterial Hb-CO, arteriovenous Hb-CO differences, and FEV1 in 58 patients with COPD and 61 ex-smoking control subjects.Arterial Hb-CO concentrations in patients at stable conditions were higher than those in control subjects (p < 0.0001). Furthermore, the Hb-CO concentrations in patients at the exacerbations (p < 0.0001) were higher than those at the stable conditions. Arterial Hb-CO concentrations in patients at stage III were higher than those in patients at stage II, and the Hb-CO concentrations in patients at stage IV were higher than those in patients at stage III at the stable conditions and exacerbations. Arterial Hb-CO correlated with exhaled CO in patients with COPD at stage II and stage III at the exacerbations. Arterial Hb-CO inversely correlated with the arterial blood partial oxygen pressure and FEV1. Arteriovenous Hb-CO differences in patients at the exacerbations did not differ from those in patients at stable conditions and from those in control subjects. Moreover, arterial Hb-CO correlated with serum C-reactive protein values and serum lipid peroxide concentrations.These findings suggest that increased arterial Hb-CO may relate to severity in patients with COPD because of lung and systemic inflammation and production of reactive oxygen species.
DLC1 Negatively Regulates Angiogenesis in a Paracrine Fashion
Authors: Yi-Ping Shih, Yi-Chun Liao, Yuan Lin, Su Hao Lo
Journal: Cancer Research (2010)

The Rho GTPase-activating protein DLC1 is a tumor suppressor that is often deleted in liver cancer and downregulated in other cancers. DLC1 regulates the actin cytoskeleton, cell shape, adhesion, migration, and proliferation through its Rho GTPase-activating protein activity and focal adhesion localization. In this study, we silenced DLC1 in nonmalignant prostate epithelial cells to explore its tumor suppression functions. Small hairpin RNA-mediated silencing of DLC1 was insufficient to promote more aggressive phenotypes associated with tumor cell growth. In contrast, DLC1 silencing promoted pro-angiogenic responses through vascular endothelial growth factor (VEGF) upregulation, accompanied by the accumulation of hypoxia-inducible factor 1α and its nuclear localization. Notably, modulation of VEGF expression by DLC1 was dependent on epidermal growth factor receptor-MAP/ERK kinase-hypoxia-inducible factor 1 signaling but on RhoA pathways. Clinically, VEGF upregulation is a highly significant event in prostate cancers in which DLC1 is downregulated. Thus, our results strongly suggest that loss of DLC1 may serve as a "second hit" in promoting angiogenesis in a paracrine fashion during tumorigenesis.
S96 Survival after the first myocardial infarction is shorter in patients with COPD compared to the general population
Authors: J. K. Quint, E. Herrett, A. Timmis, H. Hemingway, L. Smeeth
Journal: Thorax (2011)

<h3>Background</h3> Patients with COPD are at increased risk of myocardial infarction (MI) compared to the general population and have shorter survival after any MI. We investigated whether this held true in patients with an "unanticipated" MI, defined as an MI occurring as the first manifestation of atherosclerotic disease <i>and</i> without any traditional cardiovascular risk factors <i>and</i> without any prior chest pain. <h3>Methods</h3> All patients experiencing their first MI between 1st January 2003 and 31st December 2008 as recorded in Myocardial Ischaemia National Audit Project (MINAP), who had no previous evidence of MI in their General Practice Research Database (GPRD) or MINAP record were included. Patients under 18 years of age, not registered with GPRD at the time of MI, or with &lt;1 year of standard follow-up before their MI were excluded. Data were provided by the "Cardiovascular Disease Research Linking Bespoke Cohorts and Electronic Records" (CALIBER) group at UCL. The primary exposure of interest was diagnosis of COPD (defined in GPRD) and the outcome death after MI. Survival analysis was done using Kaplan–Meier methods. Cox proportional hazards models were used to adjust for potential confounders (age and sex). <h3>Results</h3> 8065 individuals were included, 968 (12%) of whom had a physician diagnosis of COPD made either before the first MI or during the follow-up period. 87 patients died on the day of admission 10 (11.5%) of whom had COPD. The overall mortality rate was 160.2 deaths (95%CI 145.5 to 176.5) per 1000 person years in those with COPD compared to 99.4 deaths (95.2 to 103.9) per 1000 person years in those without COPD. After adjusting for confounding by sex and stratifying for age, survival was shorter after 1st MI in patients with COPD; HR 1.37 (1.23 to 1.52, p&lt;0.001) in those with COPD compared to those without COPD (Abstract S96 figure 1). Survival was shorter in those (n=96) who exacerbated within 6 months of their 1st MI; HR 1.72 (1.13 to 2.60, p=0.01). <h3>Conclusions</h3> Survival is shorter after an "unanticipated" MI in patients with COPD and patients who exacerbate within 6 months of their MI have an even higher mortality rate.
Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.
Authors: J T Hunter, M P Ashley, S Sukumar, T Sugimoto, B Zbar, H J Rapp, E Yarkoni
Journal: The Journal of Experimental Medicine (1981)

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.
Decision to dissolve troubled London trust prompts anger from neighbouring clinicians
Authors: A. O'Dowd
Journal: BMJ (2013)

Final proposals for a London NHS trust with large debts to be dissolved and its services allocated elsewhere have prompted strong opposition from local doctors and other healthcare staff from a neighbouring trust.

The final report on the South London Healthcare NHS Trust by the government appointed trust special administrator was published on 8 January,1 setting out its proposals on how to deal with the trust, which has a deficit of more than £1m a week and a predicted accumulated deficit of £207m (€254m; $332m) by the end of the current financial year.

The controversial proposals for the trust, which encompasses Queen Mary’s Hospital in Sidcup, Princess Royal University Hospital near Orpington, and Queen Elizabeth Hospital in Woolwich, say that the trust does not have a viable future and should be dissolved, with services being broken up.

The new report was drawn up by Matthew Kershaw, the trust special administrator, and a team of senior doctors, nurses, and health experts and advisers.

Kershaw was appointed last July by the then health secretary, Andrew Lansley, under the regime for unsustainable NHS providers, the first time this power has been used since its introduction in 2009. The new report confirms recommendations made in a draft report published in October last year. …
Bioflavonoid Quercetin Inhibits Interleukin-1-Induced Transcriptional Expression of Monocyte Chemoattractant Protein-1 in Glomerular Cells via Suppression of Nuclear Factor-κB
Authors: YOSHIHISA ISHIKAWA, HITOSHI SUGIYAMA, ELENI STYLIANOU, MASANORI KITAMURA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Flavonoids are semiessential food components that possess anti-inflammatory properties. This report describes a novel potential of bioflavonoid quercetin as an inhibitor of monocyte chemoattractant protein-1 (MCP-1) in glomerular cells. Cultured mesangial cells as well as isolated glomeruli expressed MCP-1 mRNA in response to interleukin-1β (IL-1β). Quercetin dramatically inhibited the cytokine-triggered MCP-1 expression. To explore the mechanisms involved, effects of quercetin on the putative transcriptional activators of MCP-1, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), were examined. Exposure of the cells to IL-1β caused activation of NF-κB without significant upregulation of AP-1 activity. NF-κB inhibitor MG132 diminished the IL-1-induced expression of MCP-1 in mesangial cells and isolated glomeruli, whereas c-Jun/Ap-1 inhibitor curcumin did not affect this process. Consistently, NF-κB-inactive mesangial cells expressing a super-repressor mutant of IκBα showed blunted expression of MCP-1 by IL-1β. In contrast, AP-1-inactive mesangial cells expressing a dominant-negative mutant of c-Jun exhibited the same level of MCP-1 mRNA as that in control cells. These results suggest that: (1) quercetin has the ability to attenuate activation of NF-κB; and (2) it inhibits IL-1-triggered MCP-1 expression via suppression of NF-κB, but not AP-1, in glomerular cells.