tbuckley/cabot-search huggingface dataset:
Passive smoking exposure is associated with an increased risk of COPD
Authors: A Nataraja
Journal: Thorax (2008)

More than 15% of patients with chronic obstructive pulmonary disease (COPD) are never smokers. This study attempted to correlate passive smoking exposure with the risk of developing COPD in a South Chinese population.

Participants were drawn from the Biobank cohort of over 100 000 Guangzhou residents. The study group comprised 6497 never smokers aged …
A5.13 Effect of Rituximab on B Cell Subpopulations Expressing the 9G4 Idiotype in Patients with Rheumatoid Arthritis
Authors: Rita A Moura, Inmaculada de la Torre, Maria J Leandro, Geraldine Cambridge
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Antibodies encoded by the V<sub>H</sub>4–34 gene are inherently autoreactive, binding to red blood cell determinants. An idiotope present on the majority of immunoglobulins derived from the V<sub>H</sub>4–34 gene can be detected using the rat monoclonal antibody 9G4. 9G4 also allows the detection of B cells expressing B cell receptors derived from V<sub>H</sub>4–34 gene. We therefore determined the effect of B cell depletion therapy with rituximab (RTX) on B cell subpopulations expressing the 9G4 idiotype in peripheral blood of patients with rheumatoid arthritis (RA) as a means of following the fate of a specific autoreactive B cell population. <h3>Materials and Methods</h3> B-cell subpopulations were characterised by flow cytometry using combinations of IgD, CD5, CD27 and CD38 in healthy controls (HC) (n = 7), patients with RA before (n = 10) and at clinical relapse after RTX (n = 17). The frequency of each 9G4+ B cell subpopulation was calculated after gating on 9G4+ cells. <h3>Results</h3> No significant differences were observed in the frequency of total 9G4+ B cells between both patient groups and HC, although the levels of 9G4+ B cells tended to be higher at relapse after RTX treatment. After RTX treatment, repopulating total B cells were predominantly transitional (IgD+CD38++) and naïve (IgD+CD38+), with lower frequencies of most memory B-cell subpopulations. At relapse, RA patients had significantly more 9G4+IgD−CD38− memory B cells compared to HC. This B cell subset was positively correlated with a 9G4+CD5+CD27+ subpopulation. The frequency of 9G4+IgD–CD38+ memory B cells also tended to be increased after RTX compared to HC and pre-RTX. Lower levels of 9G4+IgD+CD38+ naïve, 9G4+IgD+CD38– memory and 9G4+CD5–CD27+ memory B cells were found after RTX treatment compared with HC and pre-RTX. No significant differences were observed in 9G4+IgD+CD38++ transitional, or 9G4+IgD–CD38++ plasmablasts in RA patients before and after RTX treatment in comparison with HC. However, there was a positive correlation between the frequency of 9G4+IgD–CD38++ plasmablasts and time after RTX treatment. <h3>Conclusions</h3> Alterations in the frequency of memory B cell subpopulations expressing 9G4 idiotype occur in clinically relapsing RA patients after RTX treatment, particularly in IgD–CD38– memory B cell subset. It is possible that this 9G4+ B cell subpopulation escapes B cell depletion therapy, being rescued in niches such as secondary lymphoid organs, or in inflammatory sites. Our results also suggest that the normal tolerance mechanisms preventing 9G4+ B cells from becoming antibody producing cells is defective in patients with RA.
Intracoronary thrombectomy improves myocardial reperfusion in patients undergoing direct angioplasty for acute myocardial infarction
Authors: Massimo Napodano, Giampaolo Pasquetto, Salvatore Saccà, Carlo Cernetti, Virginia Scarabeo, Pietro Pascotto, Bernhard Reimers
Journal: Journal of the American College of Cardiology (2003)
Inhibitory Effects of Insulin on Cytosolic Ca <sup>2+</sup> Level and Contraction in the Rat Aorta
Authors: Shu-Zhong Han, Yasuyoshi Ouchi, Hideaki Karaki, Hajime Orimo
Journal: Circulation Research (1995)

Abstract To determine the mechanism of the inhibitory effect of insulin on vascular tone, contraction was measured simultaneously with endothelial and smooth muscle cytosolic Ca 2+ level ([Ca 2+ ] i ) in the isolated rat aorta. Insulin (200 mU/mL) increased endothelial [Ca 2+ ] i and decreased resting muscle tone. The removal of endothelium abolished the effects of insulin. In the aorta precontracted with norepinephrine, insulin (3 to 120 mU/mL) induced concentration-dependent inhibition of contraction. The relaxant effect followed the increase in endothelial [Ca 2+ ] i and decrease in smooth muscle [Ca 2+ ] i . The relaxant effect was attenuated by removal of endothelium or by the addition of 10 −5 mol/L N G -monomethyl- l -arginine but not by 10 −5 mol/L indomethacin. In the absence of endothelium, the relaxant effect of insulin followed the decrease in smooth muscle [Ca 2+ ] i . These results suggest that insulin inhibits vascular contraction by dual mechanisms in the isolated rat aorta: (1) Insulin acts on vascular endothelium by increasing endothelial [Ca 2+ ] i and releasing NO, which decreases smooth muscle [Ca 2+ ] i and the Ca 2+ sensitivity of the contractile elements. (2) Insulin also directly acts on smooth muscle and decreases smooth muscle [Ca 2+ ] i .
Risk factors for injuries in male professional soccer: a systematic review
Authors: J P Stege, J H Stubbe, E A L M Verhagen, W van Mechelen
Journal: British Journal of Sports Medicine (2011)

Background Risk for injury in professional soccer is one of the largest in sports. Next to negative aspects for players' health, in professional soccer the absence of players due to injury leads to high costs. Therefore it is important to gain knowledge on injury risk factors within this specific athletic population to draw up measures that may prevent injuries. Objective To systematically review intrinsic and extrinsic risk factors which are related to injuries in male professional soccer players. Design A computerised literature search was carried out in Medline, Embase, SportDiscus and PsycInfo to search for relevant original studies. A study was included if: (1) it contained data of professional, adult, male soccer players; (2) it concerned a prospective or retrospective cohort study covering at least half a season; (3) it addressed data of at least one team; (4) it assessed risk factors for injuries. All relevant studies were assessed for quality. Results In total 313 articles were found, of which 14 were identified as being relevant and of sufficient methodological quality. In total 14 potential intrinsic and nine potential extrinsic risk factors were investigated in the included studies. From these, previous injury, preseason strength imbalances, decreased muscle flexibility and a preseason ultrasonic abnormality in the Achilles tendon were reported in the literature as intrinsic risk factors for injury. With regard to extrinsic risk factors artificial turf, match result, and time of the season were associated with injury occurrence. Conclusion To date, aetiological studies in professional soccer have mainly charted player characteristics, for example, age, playing position, strength, and ankle stability. According to the literature 23 potential risk factors have been investigated, and only seven have been associated with the occurrence of injury. Future research should further explore modifiable extrinsic risk factors, and translate ascertained factors into practical preventive efforts.
Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro
Authors: Sandra March, Elliot E. Hui, Gregory H. Underhill, Salman Khetani, Sangeeta N. Bhatia
Journal: Hepatology (2009)

Abstract Liver sinusoidal endothelial cells (LSECs) differ, both structurally and functionally, from endothelial cells (ECs) lining blood vessels of other tissues. For example, in contrast to other ECs, LSECs possess fenestrations, have low detectable levels of platelet endothelial cell adhesion molecule 1 expression, and in rat tissue, they distinctively express a cell surface marker recognized by the SE-1 antibody. These unique phenotypic characteristics seen in hepatic tissue are lost over time upon culture in vitro; therefore, this study sought to systematically examine the effects of microenvironmental stimuli—namely, extracellular matrix and neighboring cells, on the LSEC phenotype in vitro . In probing the role of the underlying extracellular matrix, we identified collagen I and collagen III as well as mixtures of collagen I/collagen IV/fibronectin as having a positive effect on LSEC survival. Furthermore, using a stable hepatocellular model (hepatocyte–fibroblast) we were able to prolong the expression of both SE-1 and phenotypic functions of LSEC such as factor VIII activity and AcLOL uptake in cocultured LSECs through the production of short-range paracrine signals. In the course of these experiments, we identified the antigen recognized by SE-1 as CD32b. Conclusion: Collectively, this study has identified several microenvironmental regulators of liver sinusoidal endothelial cells that prolong their phenotypic functions for up to 2 weeks in culture, enabling the development of better in vitro models of liver physiology and disease. (Hepatology 2009.)
EXPERIMENTAL BRONCHOPNEUMONIA BY INTRABRONCHIAL INSUFFLATION
Authors: Martha Wollstein, S. J. Meltzer
Journal: The Journal of Experimental Medicine (1912)

When intrabronchial insufflation of pure cultures of the streptococcus or of the influenza bacillus is properly carried out, it produces without fail a pneumonic lesion. This lesion is similar in its nature to the one known in human pathology as bronchopneumonia, and differs materially from the pneumonic lesion produced experimentally by the intrabronchial insufflation of pure cultures of the pneumococcus. Considering the fact that none of the dogs used in the experiments with the pneumococcus and none of those used in the present investigation were selected or prepared in any way, the conclusion seems to be unavoidable that the proper invasion of the microörganism is the determining factor in the development of pneumonia, the condition of the animal being only a minor element in this regard. Furthermore, since different organisms introduced in the same way and under conditions which are apparently the same produced distinctly different pneumonic lesions in animals of the same species, the further conclusion presents itself that the different types of pneumonia are produced by specifically different bacteria. However, further investigation may show that the differences in the nature of the lesion are due rather to the degree of virulence of the causative microörganism than to differences in the species; that is, that different lesions may possibly be produced by organisms of the same species, provided they possess different degrees of virulence. Further experimentation may also show that the condition of the animal and of the affected organ which, in the onset and development of the pneumonic disease, is, perhaps, unimportant, may be the leading factor in determining the course and outcome of the disease.
Statistical Foundations for Model-Based Adjustments
Authors: Sander Greenland, Neil Pearce
Journal: Annual Review of Public Health (2015)

Most epidemiology textbooks that discuss models are vague on details of model selection. This lack of detail may be understandable since selection should be strongly influenced by features of the particular study, including contextual (prior) information about covariates that may confound, modify, or mediate the effect under study. It is thus important that authors document their modeling goals and strategies and understand the contextual interpretation of model parameters and model selection criteria. To illustrate this point, we review several established strategies for selecting model covariates, describe their shortcomings, and point to refinements, assuming that the main goal is to derive the most accurate effect estimates obtainable from the data and available resources. This goal shifts the focus to prediction of exposure or potential outcomes (or both) to adjust for confounding; it thus differs from the goal of ordinary statistical modeling, which is to passively predict outcomes. Nonetheless, methods and software for passive prediction can be used for causal inference as well, provided that the target parameters are shifted appropriately.
The Ankle Brachial Index Is Associated with Leg Function and Physical Activity: The Walking and Leg Circulation Study
Authors: Mary McGrae McDermott, Philip Greenland, Kiang Liu, Jack M. Guralnik, Lillian Celic, Michael H. Criqui, Cheeling Chan, Gary J. Martin, Joseph Schneider, William H. Pearce, Lloyd M. Taylor, Elizabeth Clark
Journal: Annals of Internal Medicine (2002)

The ankle brachial index (ABI) is a noninvasive, reliable measure of lower-extremity ischemia. However, the relationship between ABI and lower-extremity function has not been well studied.To describe the association between the ABI and lower-extremity function.Cross-sectional study.3 academic medical centers in the Chicago area.740 men and women (460 with peripheral arterial disease).Accelerometer-measured physical activity over 7 days, 6-minute walk, 4-m walking velocity, standing balance, and ABI.33% of participants with peripheral arterial disease had intermittent claudication. Fewer than 40% of participants with an ABI less than 0.40 walked continuously for 6 minutes compared with more than 95% of participants with an ABI between 1.00 and 1.50. Compared with an ABI of 1.10 to 1.50, an ABI less than 0.50 was associated with shorter distance walked in 6 minutes (beta-regression coefficient = -523 ft [95% CI, -592 to -454 ft]; P < 0.001), less physical activity (beta = -514.8 activity units [CI, -657 to -373 activity units]; P < 0.001), slower 4-m walking velocity (beta = -0.21 m/s [CI, -0.27 to -0.15 m/s]; P < 0.001), and less likelihood of maintaining a tandem stand for 10 seconds (odds ratio, 0.37 [CI, 0.18 to 0.76]; P = 0.007), after adjustment for typical confounders. Associations between ABI and function were stronger than associations between leg symptoms and function.The ABI, a noninvasive test that can be performed in a medical office, is more closely associated with leg function in persons with peripheral arterial disease than is intermittent claudication or other leg symptoms. These data support the use of the ABI to identify abnormal lower-extremity function.
The modern diagnosis and management of pleural effusions
Authors: Rahul Bhatnagar, Nick Maskell
Journal: BMJ (2015)

#### The bottom line

A pleural effusion describes an excess of fluid in the pleural cavity, usually resulting from an imbalance in the normal rate of pleural fluid production or absorption, or both. Pleural effusions are common, with an estimated 1-1.5 million new cases in the United States and 200 000-250 000 in the United Kingdom each year.1 This review describes how pleural effusions may be investigated and treated in the community and secondary care, with a particular focus on the emerging phenomenon of ambulatory management.

#### Sources and selection criteria

We searched through PubMed, Embase, Medline, and the Cochrane database of systematic reviews from inception to April 2015 using the primary search terms “pleural effusion” and “indwelling pleural catheter”. We included abstracts published in English and related to adults. Priority was given to randomised controlled trials and meta-analyses, although citations from case series and retrospective studies have been included where appropriate. Further information was obtained from our personal libraries, trial registration databases (such as www.isrctn.com), and conference proceedings where necessary.

More than 50 causes of pleural effusions …
A Case–Control Study of Levothyroxine and the Risk of Colorectal Cancer
Authors: Gad Rennert, Hedy S. Rennert, Mila Pinchev, Stephen B. Gruber
Journal: JNCI Journal of the National Cancer Institute (2010)

Levothyroxine is a synthetic T 4 hormone commonly used to treat thyroid disease. Increased incidence of mostly autoimmune thyroid disease has been associated with breast and other malignancies, and thyroid hormone levels might also be associated with risk of colorectal cancer (CRC). In this population-based matched case–control study (2566 pairs) of CRC in northern Israel, use of levothyroxine for at least 5 years was assessed using structured interviews and validated by prescription records. The analysis included use of statins, aspirin, and hormone replacement therapy; CRC family history; physical activity; vegetable consumption; ethnicity; age; and sex. All statistical tests were two-sided. The use of levothyroxine was associated with a statistically significantly reduced relative risk of CRC (odds ratio = 0.59, 95% confidence interval = 0.43 to 0.82, P = .001). This association remained statistically significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of CRC, ethnic group, and level of vegetable consumption (odds ratio = 0.60, 95% confidence interval = 0.44 to 0.81, P = .001). No statistically significant interactions were seen between use of levothyroxine and aspirin, statins, or hormone replacement therapy.
The Critical Role of Neutral Cholesterol Ester Hydrolase 1 in Cholesterol Removal From Human Macrophages
Authors: Masaki Igarashi, Jun-ichi Osuga, Hiroshi Uozaki, Motohiro Sekiya, Shuichi Nagashima, Manabu Takahashi, Satoru Takase, Mikio Takanashi, Yongxue Li, Keisuke Ohta, Masayoshi Kumagai, Makiko Nishi, Masakiyo Hosokawa, Christian Fledelius, Poul Jacobsen, Hiroaki Yagyu, Masashi Fukayama, Ryozo Nagai, Takashi Kadowaki, Ken Ohashi, Shun Ishibashi
Journal: Circulation Research (2010)

Hydrolysis of intracellular cholesterol ester (CE) is the key step in the reverse cholesterol transport in macrophage foam cells. We have recently shown that neutral cholesterol ester hydrolase (Nceh)1 and hormone-sensitive lipase (Lipe) are key regulators of this process in mouse macrophages. However, it remains unknown which enzyme is critical in human macrophages and atherosclerosis.We aimed to identify the enzyme responsible for the CE hydrolysis in human macrophages and to determine its expression in human atherosclerosis.We compared the expression of NCEH1, LIPE, and cholesterol ester hydrolase (CES1) in human monocyte-derived macrophages (HMMs) and examined the effects of inhibition or overexpression of each enzyme in the cholesterol trafficking. The pattern of expression of NCEH1 was similar to that of neutral CE hydrolase activity during the differentiation of HMMs. Overexpression of human NCEH1 increased the hydrolysis of CE, thereby stimulating cholesterol mobilization from THP-1 macrophages. Knockdown of NCEH1 specifically reduced the neutral CE hydrolase activity. Pharmacological inhibition of NCEH1 also increased the cellular CE in HMMs. In contrast, LIPE was barely detectable in HMMs, and its inhibition did not decrease neutral CE hydrolase activity. Neither overexpression nor knockdown of CES1 affected the neutral CE hydrolase activity. NCEH1 was expressed in CD68-positive macrophage foam cells of human atherosclerotic lesions.NCEH1 is expressed in human atheromatous lesions, where it plays a critical role in the hydrolysis of CE in human macrophage foam cells, thereby contributing to the initial part of reverse cholesterol transport in human atherosclerosis.
Hypothalamic PI3K and MAPK differentially mediate regional sympathetic activation to insulin
Authors: Kamal Rahmouni, Donald A. Morgan, Gina M. Morgan, Xuebo Liu, Curt D. Sigmund, Allyn L. Mark, William G. Haynes
Journal: Journal of Clinical Investigation (2004)

The action of insulin in the central nervous system produces sympathetic nervous system activation (also called sympathoactivation), although the neuronal intracellular mechanisms that mediate this are unclear. We hypothesized that PI3K and MAPK, the major pathways involved in insulin receptor signaling, mediate sympathetic nerve responses to insulin. Intracerebroventricular administration of insulin in rat increased multifiber sympathetic nerve activity to the hindlimb, brown adipose tissue (BAT), adrenal gland, and kidney. Ex vivo biochemical studies of mediobasal hypothalamic tissue revealed that insulin stimulated the association of insulin receptor substrate–1 with the p85α subunit of PI3K and also tyrosine phosphorylation of p42 and p44 subunits of MAPK in the hypothalamus. In order to determine whether PI3K and/or MAPK were involved in insulin-mediated sympathoactivation, we tested the effect of specific inhibitors of PI3K (LY294002 and wortmannin) and MAPK (PD98059 and U0126) on regional sympathetic responses to insulin. Interestingly, regional sympathoactivation to insulin was differentially affected by blockade of PI3K and MAPK. Inhibition of PI3K specifically blocked insulin-induced sympathoactivation to the hindlimb, while inhibition of MAPK specifically blocked insulin-induced sympathoactivation to BAT. Sympathoactivation to corticotrophin-releasing factor, however, was not affected by inhibition of PI3K and MAPK. These data demonstrate that PI3K and MAPK are specific and regionally selective mediators of the action of insulin on the sympathetic nervous system.
Prevalence and Risk Factors for Homelessness and Utilization of Mental Health Services Among 10,340 Patients With Serious Mental Illness in a Large Public Mental Health System
Authors: David P. Folsom, William Hawthorne, Laurie Lindamer, Todd Gilmer, Anne Bailey, Shahrokh Golshan, Piedad Garcia, Jürgen Unützer, Richard Hough, Dilip V. Jeste
Journal: American Journal of Psychiatry (2005)

The authors examined the prevalence of and risk factors for homelessness among all patients treated for serious mental illnesses in a large public mental health system in a 1-year period. The use of public mental health services among homeless persons was also examined.The study included 10,340 persons treated for schizophrenia, bipolar disorder, or major depression in the San Diego County Adult Mental Health Services over a 1-year period (1999-2000). Analytic methods that adjusted for potentially confounding variables were used. Multivariate logistic regression analyses were used to calculate odds ratios for the factors associated with homelessness, including age, gender, ethnicity, substance use disorder, Medicaid insurance, psychiatric diagnosis, and level of functioning. Similarly, odds ratios were computed for utilization of mental health services by homeless versus not-homeless patients.The prevalence of homelessness was 15%. Homelessness was associated with male gender, African American ethnicity, presence of a substance use disorder, lack of Medicaid, a diagnosis of schizophrenia or bipolar disorder, and poorer functioning. Latinos and Asian Americans were less likely to be homeless. Homeless patients used more inpatient and emergency-type services and fewer outpatient-type services.Homelessness is a serious problem among patients with severe mental illness. Interventions focusing on potentially modifiable factors such as substance use disorders and a lack of Medicaid need to be studied in this population.