tbuckley/cabot-search huggingface dataset:
Study of adherence to the use of inhaled sodium colistimethate through the I-neb® nebulization system
Authors: Abel Trujillano Ruiz, María Jesús Avilés Inglés, María Teresa Antequera Lardón, Juan José Franco Miguel, Carmen Caballero Requejo, Lorena Rentero Redondo, Celia Gracía-Molina Sáez, Blanca Medina Tovar, Elena Urbieta Sanz
Journal: European Respiratory Journal (2014)

OBJECTIVE  To relate the adherence to treatment with inhaled sodium colistimethate(ISC)with the efficacy in patients with non-cystic fibrosis(CF)bronchiectasis colonized with  Pseudomonas aeruginosa (PA)  MATERIAL AND METHODS  Retrospective observational study conducted from January 2010 until December 2013.We selected patients who started treatment with ISC.Data was obtained from the inhalation I-neb®device(IND)such as average duration of the complete treatments, management of the device and the adhesion of the first 2 months of continuous treatment.We obtained demographic,diagnostic and microbiological data,considering in each case whether it was initial colonization,intermittentor chronic  RESULTS  Of all patients treated with ISC, 16 of them met the conditions to be included in the study as they could be monitored with the IND.The average age was 69.5 years(SD: 18.4),and 56.3%were men.Regarding the type of colonization it was initial in 5 patients,intermittent in 1 and chronic in 9.The data from the IND were:1-An average duration of complete treatments of 6.3 minutes (SD:4.2)2-A proper handling of the device of 95%.3- An adherence to treatment of 93.8%.After the completion of treatment cultures were negativized in 8 patients(4 had initial colonization and 4 chronic)  CONCLUSIONS  Most of the patients are adherent to the treatment, reach a suitable medium inhalation time and good management of the device, which demonstrates the ease of use of the IND  The proportion of patients with initial colonization whose cultures became negative was high(80%),demonstrating that a good adherence along with an early beginning of treatment increases the probability of eradicating PA.
Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice
Authors: J. D. Belcher
Journal: Journal of Clinical Investigation (2006)

Transgenic sickle mice expressing βS hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-κB and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation–induced stasis, leukocyte-endothelium interactions, and NF-κB, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-κB, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation–induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.
The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort
Authors: Manuel F Ugarte-Gil, Eduardo Acevedo-Vásquez, Graciela S Alarcón, Cesar A Pastor-Asurza, José L Alfaro-Lozano, Jorge M Cucho-Venegas, Maria I Segami, Daniel Wojdyla, Enrique R Soriano, Cristina Drenkard, João Carlos Brenol, Ana Carolina de Oliveira e Silva Montandon, Lilian T Lavras Costallat, Loreto Massardo, José F Molina-Restrepo, Marlene Guibert-Toledano, Luis H Silveira, Mary Carmen Amigo, Leonor A Barile-Fabris, Rosa Chacón-Díaz, Maria H Esteva-Spinetti, Guillermo J Pons-Estel, Gerald McGwin, Bernardo A Pons-Estel
Journal: Annals of the Rheumatic Diseases (2014)

Purpose To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. Methods SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. Results 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p&lt;0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate). Conclusions The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.
Circulating Levels of Phthalate Metabolites Are Associated With Prevalent Diabetes in the Elderly
Authors: P. Monica Lind, Björn Zethelius, Lars Lind
Journal: Diabetes Care (2012)

Phthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome proliferator-activated receptors (PPARs). Because PPAR-γ agonists modulate insulin sensitivity and are used to treat type 2 diabetes, we investigated whether circulating levels of phthalate metabolites are related to prevalent type 2 diabetes.A total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer. Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a fasting plasma glucose >7.0 mmol/L.A total of 114 subjects were shown to have diabetes. Following adjustment for sex, BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01), monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05), but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence of diabetes. Using the fasting proinsulin-to-insulin ratio as a marker of insulin secretion and the homeostasis model assessment-insulin resistance index as a marker of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas MEP and MMP mainly were related to insulin resistance.The findings in this cross-sectional study showed that several phthalate metabolites are related to diabetes prevalence, as well as to markers of insulin secretion and resistance. These findings support the view that these commonly used chemicals might influence major factors that are regulating glucose metabolism in humans at the level of exposure of phthalate metabolites seen in the general elderly population.
Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis
Authors: C. Costelloe, C. Metcalfe, A. Lovering, D. Mant, A. D. Hay
Journal: BMJ (2010)

<h3>Objectives</h3> The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC. <h3>Design</h3> A total of 98 samples were sequenced to a mean depth of 31 642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies. <h3>Results</h3> Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. <h3>Conclusions</h3> Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.
Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy
Authors: Albena Jordanova, Joy Irobi, Florian P Thomas, Patrick Van Dijck, Kris Meerschaert, Maarten Dewil, Ines Dierick, An Jacobs, Els De Vriendt, Velina Guergueltcheva, Chitharanjan V Rao, Ivailo Tournev, Francisco A A Gondim, Marc D'Hooghe, Veerle Van Gerwen, Patrick Callaerts, Ludo Van Den Bosch, Jean-Pièrre Timmermans, Wim Robberecht, Jan Gettemans, Johan M Thevelein, Peter De Jonghe, Ivo Kremensky, Vincent Timmerman
Journal: Nature Genetics (2006)
Nephrogenic Diabetes Insipidus: Essential Insights into the Molecular Background and Potential Therapies for Treatment
Authors: Hanne B. Moeller, Søren Rittig, Robert A. Fenton
Journal: Endocrine Reviews (2013)

The water channel aquaporin-2 (AQP2), expressed in the kidney collecting ducts, plays a pivotal role in maintaining body water balance. The channel is regulated by the peptide hormone arginine vasopressin (AVP), which exerts its effects through the type 2 vasopressin receptor (AVPR2). Disrupted function or regulation of AQP2 or the AVPR2 results in nephrogenic diabetes insipidus (NDI), a common clinical condition of renal origin characterized by polydipsia and polyuria. Over several years, major research efforts have advanced our understanding of NDI at the genetic, cellular, molecular, and biological levels. NDI is commonly characterized as hereditary (congenital) NDI, arising from genetic mutations in the AVPR2 or AQP2; or acquired NDI, due to for exmple medical treatment or electrolyte disturbances. In this article, we provide a comprehensive overview of the genetic, cell biological, and pathophysiological causes of NDI, with emphasis on the congenital forms and the acquired forms arising from lithium and other drug therapies, acute and chronic renal failure, and disturbed levels of calcium and potassium. Additionally, we provide an overview of the exciting new treatment strategies that have been recently proposed for alleviating the symptoms of some forms of the disease and for bypassing G protein-coupled receptor signaling.
Social understanding and the cognitive architecture of theory of mind
Authors: Michael Siegal
Journal: Behavioral and Brain Sciences (2004)

Although Carpendale &amp; Lewis (C&amp;L) correctly emphasize the importance of conversation in children's social understanding, they neglect several complex issues. Contrary to their assertion, the focus on mental state processing has not been misplaced, and there is a need to recognize that different aspects of social understanding are liable to undergo distinctive developmental changes that vary in relation to social interaction.
Incidence of Total Knee and Hip Replacement for Osteoarthritis in Relation to Circulating Sex Steroid Hormone Concentrations in Women
Authors: Sultana Monira Hussain, Flavia M. Cicuttini, Robin J. Bell, Penelope J. Robinson, Susan R. Davis, Graham G. Giles, Stephen Graves, Roger L. Milne, Yuanyuan Wang
Journal: Arthritis & Rheumatology (2014)

Objective The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA. Methods Study subjects (n = 2,621; all women) were recruited in 1990–1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001–2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. Results During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log‐transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50–0.96), and greater log‐transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52–0.93). In contrast, greater log‐transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05–2.77). Conclusion A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA.
Neural guidance molecules, tip cells, and mechanical factors in vascular development
Authors: F. le Noble, C. Klein, A. Tintu, A. Pries, I. Buschmann
Journal: Cardiovascular Research (2008)

The vascular system is generated and maintained by reactions of blood vessels to stimuli of several types. The basic outline of the vascular system is determined during development by genetic programming, guided by the unique temporal and spatial patterns of structural and molecular features available in the embryo. With establishment of blood flow, control of vascular development is increasingly taken over by feedback signals derived from vascular function, including blood flow and pressure, in addition to those derived from the metabolic state of the tissue. Mechanical and molecular signals also govern the post-natal structural adaptation of vascular beds in response to functional requirements, both during normal, physiological conditions (growth, exercise) and during pathophysiological conditions including ischaemic diseases and tumour growth. The orderly structure of vascular beds emerges as each vessel segment reacts to the local conditions and stimuli that it experiences, according to a common set of genetically determined responses. In this process of angioadaptation, the properties and architecture of vascular beds are determined by the continuous interplay between vascular and cellular reactions to haemodynamic and molecular signals and the functional implications of these reactions, constituting a complex feedback system. Here, studies on vascular development and adaptation in response to haemodynamic and molecular factors are integrated, with emphasis on arterial-venous network development and structural adaptation of vessels.
Nicotinamide Blocks Proliferation and Induces Apoptosis of Chronic Lymphocytic Leukemia Cells through Activation of the p53/miR-34a/SIRT1 Tumor Suppressor Network
Authors: Valentina Audrito, Tiziana Vaisitti, Davide Rossi, Daniela Gottardi, Giovanni D'Arena, Luca Laurenti, Gianluca Gaidano, Fabio Malavasi, Silvia Deaglio
Journal: Cancer Research (2011)

Abstract Because of its relatively indolent clinical course, chronic lymphocytic leukemia (CLL) offers a versatile model for testing novel therapeutic regimens and drug combinations. Nicotinamide is the main NAD+ precursor and a direct inhibitor of four classes of enzymes, including the sirtuins. SIRT1, the main member of the sirtuin family, inactivates p53 by deacetylating a critical lysine residue. In this study, we showed that CLL cells express high levels of functional SIRT1, which is inhibited by exogenous nicotinamide. This agent blocks proliferation and promotes apoptosis selectively in leukemic cells that express wild-type (wt) p53. Nicotinamide modulates the p53-dependent genes p21, NOXA, BAX, and Mcl-1, indicating an activation of the p53 pathway and of caspase-3. DNA-damaging chemotherapeutics, such as etoposide, activate a functional loop linking SIRT1 and p53 through the induction of miR-34a. When leukemic cells are simultaneously exposed to nicotinamide and etoposide, we observe a significant increase in miR-34a levels with a concomitant inhibition of SIRT1. Furthermore, p53 acetylation levels are higher than with either agent used alone. Overall, treatment with both nicotinamde and etoposide shows strongly synergistic effects in the induction of apoptosis. We therefore concluded that nicotinamide has the dual property of inhibiting SIRT1 through a noncompetitive enzymatic block (p53 independent) and at the same time through miR-34a induction (p53 dependent). These observations suggested the therapeutic potential of nicotinamide, a novel, safe, and inexpensive drug, to be used in addition to chemotherapy for CLL patients with wt p53. Cancer Res; 71(13); 4473–83. ©2011 AACR.
Overlap of coronary disease and pulmonary arterial hypertension in systemic sclerosis
Authors: A Komócsi, T Pintér, R Faludi, B Magyari, J Bozó, G Kumánovics, T Minier, J Radics, L Czirják
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc). Symptoms of coronary artery disease (CAD) and PAH are closely related and cardiac catheterisation is needed to confirm their diagnosis. The aim of the present work was to investigate of the extent of overlap between CAD and PAH in patients with SSc. Methods: Based on non-invasive investigations, 20 patients out of 120 were suspected to have PAH (“suspected PAH” group). Another 10 patients showed signs of coronary disease (“suspected CAD” Group). In these 30 patients, right heart catheterisation and coronary angiography were performed, and the coronary flow reserve (CFR) was assessed by thermodilution technique. Results: In the “suspected PAH” and the “suspected CAD” groups, PAH was found in 12/20 and 2/10 cases, and coronary artery stenosis in 9/20 and 6/10 cases, respectively. Severely reduced CFR was revealed in 7/20 and 3/10 cases, respectively. Conclusions: PAH, CAD and reduced CFR all show a considerable overlap in symptomatic patients with SSc. The current non-invasive investigations are neither sensitive nor specific enough to make an appropriate distinction between these different disease manifestations. A more invasive approach, such as coronary angiography at the initial catheterisation, is required to properly characterise and treat the different forms of cardiac involvement in SSc.
Mast Cells Protect Mice from Mycoplasma Pneumonia
Authors: Xiang Xu, Dongji Zhang, Natalya Lyubynska, Paul J. Wolters, Nigel P. Killeen, Peter Baluk, Donald M. McDonald, Samuel Hawgood, George H. Caughey
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

As the smallest free-living bacteria and a frequent cause of respiratory infections, mycoplasmas are unique pathogens. Mice infected with Mycoplasma pulmonis can develop localized, life-long airway infection accompanied by persistent inflammation and remodeling.
Inconsistent Labeling of Food Effect for Oral Agents across Therapeutic Areas: Differences between Oncology and Non-Oncology Products
Authors: Soonmo Peter Kang, Mark J. Ratain
Journal: Clinical Cancer Research (2010)

Several recent oral oncology drugs were labeled for administration in fasted states despite the fact that food increases their bioavailability. Because this was inconsistent with the principles of oral drug delivery, we hypothesized that there were inconsistencies across therapeutic areas.Oral agents approved by the U.S. Food and Drug Administration from January 2000 to May 2009 were included in our study. Comparison of the food labeling patterns between oncology and non-oncology drugs was made using Fisher's exact test.Of the 99 drugs evaluated, 34 showed significant food effects on bioavailability. When food markedly enhanced bioavailability, eight out of nine non-oncology drugs were labeled "fed" to take advantage of the food-drug interaction, whereas all oncology drugs (n = 3) were labeled to be administered in "fasted" states (Fisher's exact test, P = 0.01).Drug labeling patterns with respect to food-drug interactions observed with oncology drugs are in contradiction with fundamental pharmacologic principles, as exemplified in the labeling of non-oncology drugs. .