tbuckley/cabot-search huggingface dataset:
Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years
Authors: A E Tattersfield
Journal: Thorax (2001)

Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment.Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism.Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck.In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.
The multiple adaptive problems solved by human aggression
Authors: David M. Buss
Journal: Behavioral and Brain Sciences (2009)

Abstract Human psychology contains adaptations to deploy aggression as one solution to many distinct adaptive problems. These include expropriating resources, defending against incursions, establishing encroachment-deterring reputations, inflicting costs on rivals, ascending dominance hierarchies, dissuading partner defection, eliminating fitness-draining offspring, and obtaining new mates. Aggression is not a singular strategy. Comprehensive theories must identify the “design features” of multiple adaptations for aggression.
Biomarker Modulation following Short-Term Vorinostat in Women with Newly Diagnosed Primary Breast Cancer
Authors: Vered Stearns, Lisa K. Jacobs, MaryJo Fackler, Theodore N. Tsangaris, Michelle A. Rudek, Michaela Higgins, Julie Lange, Zandra Cheng, Shannon A. Slater, Stacie C. Jeter, Penny Powers, Susanne Briest, Calvin Chao, Carl Yoshizawa, Elizabeth Sugar, Igor Espinoza-Delgado, Saraswati Sukumar, Edward Gabrielson, Nancy E. Davidson
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Agents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who received vorinostat and those who did not. Experimental Design: Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QM-MSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between pre- and post-vorinostat samples. Results: Vorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P = 0.003), STK15 (P = 0.005), and Cyclin B1 (P = 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed. Conclusions: Short-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports investigation of vorinostat in combination with other agents for the management of breast cancer. Clin Cancer Res; 19(14); 4008–16. ©2013 AACR.
Rapid Effector Function in CD8+ Memory T Cells
Authors: Ajit Lalvani, Roger Brookes, Sophie Hambleton, Warwick J. Britton, Adrian V.S. Hill, Andrew J. McMichael
Journal: The Journal of Experimental Medicine (1997)

The nature of the CD8+ T cells that underlie antiviral protective immunological memory in vivo is unclear. We have characterized peptide-specific CD8+ T lymphocytes directly ex vivo from peripheral blood in humans with past exposure to influenza virus, using single cell interferon γ (IFN-γ) release as a measure of effector function. In individuals in the memory state with respect to influenza virus infection, unrestimulated antigen-specific CD8+ T cells displayed IFN-γ release within 6 h of antigen contact, identifying a population of memory CD8+ T cells that exhibit effector function without needing to divide and differentiate over several days. We have quantified circulating CD8+ effector T cells specific for six different MHC class I–restricted influenza virus epitopes. Enumeration of these CD8+ T cells gives frequencies of peptide-specific T cells that correlate with, but are in general severalfold higher than, CTL precursor frequencies derived from limiting dilution analysis, indicating that this novel population of memory CD8+ T cells has hitherto been undetected by standard means. The phenotype of these cells, which persist at a low frequency long after recovery from an acute viral infection, suggests that they play a role in protective immunological memory.
Improving RNA-Seq expression estimates by correcting for fragment bias
Authors: Adam Roberts, Cole Trapnell, Julie Donaghey, John L Rinn, Lior Pachter
Journal: Genome biology (2011)

Abstract The biochemistry of RNA-Seq library preparation results in cDNA fragments that are not uniformly distributed within the transcripts they represent. This non-uniformity must be accounted for when estimating expression levels, and we show how to perform the needed corrections using a likelihood based approach. We find improvements in expression estimates as measured by correlation with independently performed qRT-PCR and show that correction of bias leads to improved replicability of results across libraries and sequencing technologies.
Should Left Ventricular Assist Device Should Be Standard of Care for Patients With Refractory Heart Failure Who Are Not Transplantation Candidates?
Authors: Mandeep R. Mehra, Michael J. Domanski
Journal: Circulation (2012)

development of current mechanical circulatory sup- port (MCS) systems began in the 1960s as an effort to provide a therapeutic option for patients with refractory advanced heart failure. 1 Today, MCS represents a viable alternative to cardiac transplantation for the overwhelming majority of patients in whom age, comorbidities, or the profound shortage of donors makes transplantation infeasible.
Atherogenic Lipids and Endothelial Dysfunction: Mechanisms in the Genesis of Ischemic Syndromes
Authors: Mark R. Adams, Scott Kinlay, Gavin J. Blake, James L. Orford, Peter Ganz, Andrew P. Selwyn
Journal: Annual Review of Medicine (2000)

▪ Abstract Atherogenic lipids, particularly oxidized low-density lipoprotein, are responsible for a wide range of cellular dysfunctions within the vessel wall. The effects on endothelial cells disrupt normal control of vasomotion, with a reduction of effective nitric oxide activity, the development of a procoagulant surface, chronic low-grade inflammation, and abnormal cell growth. These changes are central not only in the development of atherosclerosis but also in the evolution of both stable and unstable ischemic syndromes. There is growing evidence that these abnormal changes in cell function respond rapidly to changes in the atherogenic lipids. Certain cell functions can improve within hours or days of cholesterol lowering.
Synthesis of Globin Chains in Sickle β-Thalassemia
Authors: Frances M. Gill, Elias Schwartz
Journal: Journal of Clinical Investigation (1973)

In five patients with sickle β-thalassemia there was balanced α- and β-globin synthesis in the bone marrow and decreased total β-chain synthesis relative to that of α-chain in the peripheral blood. These findings are similar to those in patients with simple β-thalassemia trait. Despite a range of hemoglobin concentrations from 6.8 to 12.5 g/100 ml in the patients with sickle thalassemia, there was no evidence of a significant excess of α-chains in the red cells of the bone marrow which could contribute to the hemolysis and anemia.
Transgenic Expression of Dominant-Active IDOL in Liver Causes Diet-Induced Hypercholesterolemia and Atherosclerosis in Mice
Authors: Anna C. Calkin, Stephen D. Lee, Jason Kim, Caroline M.W. Van Stijn, Xiao-Hui Wu, Aldons J. Lusis, Cynthia Hong, Rajendra I. Tangirala, Peter Tontonoz
Journal: Circulation Research (2014)

The E3 ubiquitin ligase inducible degrader of the low-density lipoprotein receptor (IDOL) triggers lysosomal degradation of the low-density lipoprotein receptor. The tissue-specific effects of the IDOL pathway on plasma cholesterol and atherosclerosis have not been examined.Given that the liver is the primary determinant of plasma cholesterol levels, we sought to examine the consequence of effect of chronic liver-specific expression of a dominant-active form of IDOL in mice.We expressed a degradation-resistant, dominant-active form of IDOL (super IDOL [sIDOL]) in C57Bl/6J mice from the liver-specific albumin promoter (L-sIDOL transgenics). L-sIDOL mice were fed a Western diet for 20 or 30 weeks and then analyzed for plasma lipid levels and atherosclerotic lesion formation. L-sIDOL mice showed dramatic reductions in hepatic low-density lipoprotein receptor protein and increased plasma low-density lipoprotein cholesterol levels on both chow and Western diets. Moreover, L-sIDOL mice developed marked atherosclerotic lesions when fed a Western diet. Lesion formation in L-sIDOL mice was more robust than in apolipoprotein E*3 Leiden mice and did not require the addition of cholate to the diet. Western diet-fed L-sIDOL mice had elevated expression of liver X receptor target genes and proinflammatory genes in their aortas.Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions. Our results show that increased activity of the IDOL pathway in the liver can override other low-density lipoprotein receptor regulatory pathways leading to cardiovascular disease. L-sIDOL mice are a robust, dominantly inherited, diet-inducible model for the study of atherosclerosis.
India's HIV prevention programme is running out of condoms
Authors: S. Cousins
Journal: BMJ (2015)

India’s HIV/AIDS prevention programme is running out of condoms, amid delays to its government funding. Some states report that they now have only a few days’ supply of condoms remaining.

India provides free condoms under its community based HIV/AIDS prevention programme that targets high risk groups, including sex workers and injecting drug users. The strategy has won praise globally, with the World Bank estimating that the country averted three million HIV infections between 1995 and 2015 as a result.

However, recently released government data show that the HIV/AIDS …
Identification of a novel TAP2 allele in a Colombian black population: gene conversion, ancestral intermediate or convergent change?
Authors: M. Carrington, J. C. Stephens, W. Y. Ma, M. Martin, A. Harding, J. Noble, H. Erlich, D. Mann, C. Arango, R. Jaramillo, M. Concha, E. Maloney, W. Blattner
Journal: Molecular Biology and Evolution (1997)

*Intramural Research Support Program, SAIC-Frederick and TNational Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland; $Human Genetics Department, Roche Molecular Systems, Alameda, California; SDepartment of Pathology, University of Maryland at Baltimore; Universidad de Valle, Cali, Colombia; TDepartment of Neurology, University of Miami; #Viral Epidemiology Branch, National Cancer Institute, Rockville, Maryland; and **Department of Medicine, University of Maryland at Baltimore
Screening older patients for obstructive airways disease in a semi-rural practice
Authors: J A Dickinson, M Meaker, M Searle, G Ratcliffe
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Obstructive airways disease in older patients is reported to be not only common, but frequently overlooked and untreated by general practitioners. This study examines the value of screening elderly patients in a large semi-rural general practice for potentially treatable asthma and chronic obstructive pulmonary disease (COPD). <h3>METHODS</h3> A random sample of 353 patients aged 60–75 years attended a nurse run screening clinic for pulmonary function testing, serial peak flow recording, and completion of a symptom questionnaire. Patients with a low forced expiratory volume in one second (below the fifth centile of their predicted value) or &gt;15% mean diurnal variation in peak flow were referred to a doctor<i>'</i>s clinic for further diagnostic assessment and/or to discuss possible treatment where appropriate. <h3>RESULTS</h3> Fifty eight patients (16.4%) had obstructive airways disease, the prevalence of asthma being 6.5% and that of COPD 9.9%. Of these, 30 had no previous diagnosis of airways disease and were not on treatment; eight of them had significant airways reversibility and 10 were current smokers. No newly diagnosed patients had severe disease as measured by pulmonary function or quality of life assessment, and six patients accepted treatment. <h3>CONCLUSION</h3> Few older patients benefited from a screening programme for obstructive airways disease in a semi-rural general practice.
Differential regulation of atrial natriuretic peptide– and adrenergic receptor–dependent lipolytic pathways in human adipose tissue
Authors: Cédric Moro, Jan Polak, Blanka Richterova, Coralie Sengenès, Terezie Pelikanova, Jean Galitzky, Vladimir Stich, Max Lafontan, Michel Berlan
Journal: Metabolism (2004)
Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis
Authors: Ying-Si Lai, Patricia Biedermann, Uwem F Ekpo, Amadou Garba, Els Mathieu, Nicholas Midzi, Pauline Mwinzi, Eliézer K N'Goran, Giovanna Raso, Rufin K Assaré, Moussa Sacko, Nadine Schur, Idrissa Talla, Louis-Albert Tchuem Tchuenté, Seydou Touré, Mirko S Winkler, Jürg Utzinger, Penelope Vounatsou
Journal: The Lancet Infectious Diseases (2015)
Assessment of dynamic humeral centering in shoulder pain with impingement syndrome: a randomised clinical trial
Authors: J. Beaudreuil, S. Lasbleiz, P. Richette, G. Seguin, C. Rastel, M. Aout, E. Vicaut, M. Cohen-Solal, F. Liote, M.-C. de Vernejoul, T. Bardin, P. Orcel
Journal: Annals of the Rheumatic Diseases (2011)

Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy. Dynamic humeral centering (DHC) aims at preventing subacromial impingement, which contributes to the disease. The goal of this study was to assess the effectiveness of DHC.69 patients with shoulder pain and impingement syndrome were prospectively included in a single-centre randomised trial with a 12-month follow-up. Patients and assessor were blinded to the study hypothesis and treatment, respectively. DHC and non-specific mobilisation as control were performed for 6 weeks, in 15 supervised individual outpatient sessions, and patients performed daily home exercises. The planned primary outcome was the Constant score including subscores for pain, activity, mobility and strength at 3 months. Secondary outcomes were the Constant score and subscores at 12 months, and medication use for pain at 3 and 12 months.The DHC group did not differ from the control group in the total Constant score at 3 months. However, the DHC group showed a higher Constant subscore for pain (12.2 (SD 2.8) vs 9.9 (2.9), least square means difference 2.1, 95% CI 0.7 to 3.5, p=0.004). At 3 months, the DHC group also showed a higher rate of no medication use (96.7% vs 71%, proportional difference 25.7, 95% CI 3.7 to 51.9, p=0.012). There was no other intergroup difference.There was no difference in the total Constant score between DHC and controls. However, pain was improved at 3 months after DHC. The differences found in subscores for pain should be explored in future studies. Trial registration clinicaltrials.gov Identifier: NCT 01022775.
Serum antioxidants and risk of rheumatoid arthritis.
Authors: M Heliovaara, P Knekt, K Aho, R K Aaran, G Alfthan, A Aromaa
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--Oxygen free radicals have been implicated as mediators of tissue damage in patients with rheumatoid arthritis (RA). Thus it is possible that several micronutrients acting as antioxidants and free radical scavengers provide protection against RA. Serum alpha-tocopherol, beta-carotene, and selenium were studied for their associations with the risk of RA. METHODS--A case control study was nested within a Finnish cohort of 1419 adult men and women. During a median follow up of 20 years, 14 individuals initially free of arthritis developed RA. Two controls per each incident case were individually matched for sex, age, and municipality. Serum alpha-tocopherol, beta-carotene and selenium concentrations were measured from stored serum samples. An antioxidant index was calculated as the product of the molar concentrations of these three micronutrients. RESULTS--Elevated risks of RA were observed at low levels of alpha-tocopherol, beta-carotene and selenium, but none of the associations were statistically significant. A significant association, however, was observed with a low antioxidant index (p for trend = 0.03), the relative risk of RA between the lowest tertile and the higher tertiles of its distribution being 8.3 (95% confidence interval 1.0-71.0). CONCLUSIONS--The results of the present study are in line with the hypothesis that a low antioxidant level is a risk factor for RA.
BAL neutrophil levels in a randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome post lung transplantation
Authors: Chris Ward, Gail Johnson, Victoria Ryan, Therese Small, James Lordan, Andrew Fisher, Gerard Meachery, Paul Corris
Journal: European Respiratory Journal (2012)

Open studies have reported an improvement in FEV1 in some BOS patients treated with Azithromycin (Azith). We recently demonstrated that Azith is superior to placebo treatment, improving FEV1 in patients with BOS. It is suggested that a BAL neutrophil reduction is associated with treatment benefit. We have investigated this in our trial.  Methods: A prospective, randomised double blind placebo controlled study of Azith 250mg o.d. or placebo on alternate days, in BOS patients. The primary outcome was change in FEV1 at 12 weeks and a secondary outcome BAL neutrophil %.  Results: 46 patients were randomised (23 Azith, 23 placebo) stratified for pre op diagnosis of suppurative disease and operation (single or bilateral lungs). Of the 46 ITT patients, baseline and final visit BAL were available for 28 (13A, 15P). In these patients the baseline % neutrophils, median (IQR), in the Azith group was 17 (4 to 69%) and in the placebo group 15 (2 to 56%). The baseline to final visit change in % neutrophils varied, with around half the patients in both treatment arms showing an increase from baseline and half a decrease. There was a median increase from baseline in the Azith group of 10%, IQR (—10% to 18%) and in the placebo group a median decrease from baseline of —1% (—8% to 5%). These changes were statistically non significant (P=0.4 and 0.7 respectively, 1-sample Wilcoxon).  Conclusion: Azith is superior to placebo improving lung function in patients with BOS. In the same patients, whilst BAL neutrophil % was high, we observed no consistent fall with Azith. This may suggest the mechanism of benefit does not rely on a quantitative reduction in neutrophils.
Airway and systemic eosinophilia in asthma: does site matter?
Authors: K. Kostikas, E. Zervas, M. Gaga
Journal: European Respiratory Journal (2014)

Asthma is a complex chronic inflammatory disorder of the airways. It involves several cell types and cellular elements, is associated with airway hyperresponsiveness, and is characterised by recurrent episodes of wheezing, breathlessness and cough. These symptoms restrict the patients’ daily activities, impact on their quality of life and, if severe and untreated, may lead to hospitalisation and death [1].

Asthma needs to be monitored and controlled, and treatment schemes follow a step-wise approach, based initially on the level of severity and then on the level of control. The assessment of asthma control includes several clinical parameters such as frequency and severity of symptoms, impact on daily activity, and use of medication. All these parameters involve the patients’ perception and are often subjective [1]. However, monitoring of airway inflammation for the evaluation of asthma control may provide objective markers of assessment but requires time and financial and technological resources. Therefore, the use of inflammatory markers in the monitoring of asthma remains highly controversial.

While the evaluation and monitoring of airway inflammation status does not seem warranted in everyday clinical management of controlled mild-to-moderate asthma, the assessment of the inflammatory phenotype is required in severe asthma that is resistant to conventional treatment, while monitoring of inflammation may help control and reduce exacerbation rates [2].

Several attempts have been made to classify patients with treatment-resistant asthma into distinct phenotypes, often involving indices of airways inflammation [3–5]. Early reports suggested that patients with more severe asthma had increased eosinophil [6] and/or neutrophil [7] counts in induced sputum and in bronchial biopsies. Although some severe asthma phenotypes and particularly inhaled corticosteroid (ICS)-resistant asthma have been associated with the presence of neutrophil predominance in sputum [6, 8], many patients …