tbuckley/cabot-search huggingface dataset:
Is air pollution of the 20th century a cause of current asthma hospitalisations?
Authors: Nino Künzli
Journal: Thorax (2011)

Danish researchers followed >57 000 older people over 10 years up to 2006.1 They made unique efforts to individually estimate exposure to traffic-related pollution for 35 years back in time, using modelled home–outdoor nitrogen dioxide (NO2) concentrations. A 5.8 μg/m3 contrast in the 35-year average NO2 concentration was associated with a 10% higher risk for a first-ever hospitalisation due to asthma. In other words, pollution of the last century appears to contribute to current hospitalisations. But does this interpretation make sense? First, I will present arguments against this conclusion. Second, I will explain how to make sense of this large and well-conducted study.

To clarify the interpretation of the results, it is worth formulating two basic hypotheses relevant to research on air pollution and chronic diseases like asthma where underlying chronic pathologies (eg, hyper-reactive airways) are superimposed by acute expressions of the chronic disease (eg, asthma attacks).2 Under this model, two primary hypotheses emerge for exposure to air pollution:

In H2, the underlying cause of the asthma cases may (H1) or may not be air pollution. While mechanisms related to the two hypotheses are not necessarily independent, there are possibly different causes and pathways involved in the two time domains of effects. For example, exposure to cold air may trigger an asthma attack, while living in a colder climate may not necessarily relate to higher incidence of asthma.

H2 has been well studied for a range of events …
Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver
Authors: Elisabetta Bugianesi, Paola Manzini, Sergio D'Antico, Ester Vanni, Filomena Longo, Nicola Leone, Paola Massarenti, Antonio Piga, Giulio Marchesini, Mario Rizzetto
Journal: Hepatology (2004)

The mechanism(s) determining the progression from fatty liver to steatohepatitis is currently unknown. Our goal was to define the relative impact of iron overload, genetic mutations of HFE, and insulin resistance on the severity of liver fibrosis in a population of subjects with nonalcoholic fatty liver disease (NAFLD) who had low prevalence of obesity and no overt symptoms of diabetes. In a cohort of 263 prospectively enrolled patients with NAFLD, 7.4% of patients had signs of peripheral iron overload and 9% had signs of hepatic iron overload, but 21.1% had hyperferritinemia. The prevalence of C282Y and H63D HFE mutations was similar to the general population and mutations were not associated with iron overload. Although subjects were on average only moderately overweight, insulin sensitivity, measured both in the fasting state and in response to oral glucose, was lower. Univariate analysis demonstrated that the presence of severe fibrosis was independently associated with older age, female sex, overweight, aspartate/alanine aminotransferase ratio, serum ferritin level, fasting glucose and insulin levels, decreased insulin sensitivity, and with histologic features (degree of necroinflammation and steatosis). After adjustment for body mass index (BMI), age, sex, and degree of steatosis, ferritin levels (odds ratio [OR] = 1.77; 95% CI = 1.21- 2.58; P =.0032) and the oral glucose insulin sensitivity (OR = 0.53; CI = 0.33-0.87; P =.0113) were independent predictors of severe fibrosis. In conclusion, the current study indicates that insulin resistance is a major, independent risk factor for advanced fibrosis in patients with NAFLD. Increased ferritin levels are markers of severe histologic damage, but not of iron overload. Iron burden and HFE mutations do not contribute significantly to hepatic fibrosis in the majority of patients with NAFLD.
Direct visualisation of collateral ventilation in COPD with hyperpolarised gas MRI
Authors: Helen Marshall, Martin H Deppe, Juan Parra-Robles, Susan Hillis, Catherine G Billings, Smitha Rajaram, Andrew Swift, Sam R Miller, Joanna H Watson, Jan Wolber, David A Lipson, Rod Lawson, Jim M Wild
Journal: Thorax (2012)

<h3>Background</h3> Collateral ventilation has been proposed as a mechanism of compensation of respiratory function in obstructive lung diseases but observations of it in vivo are limited. The assessment of collateral ventilation with an imaging technique might help to gain insight into lung physiology and assist the planning of new bronchoscopic techniques for treating emphysema. <h3>Objective</h3> To obtain images of delayed ventilation that might be related to collateral ventilation over the period of a single breath-hold in patients with chronic obstructive pulmonary disease (COPD). <h3>Methods</h3> Time-resolved breath-hold hyperpolarised <sup>3</sup>He MRI was used to obtain images of the progressive influx of polarised gas into initially non-ventilated defects. <h3>Results</h3> A time-series of images showed that <sup>3</sup>He moves into lung regions which were initially non-ventilated. Ventilation defects with delayed filling were observed in 8 of the 10 patients scanned. <h3>Conclusions</h3> A method for direct imaging of delayed ventilation within a single breath-hold has been demonstrated in patients with COPD. Images of what is believed to be collateral ventilation and slow filling of peripheral airspaces due to increased flow resistance are presented. The technique provides 3D whole-lung coverage with sensitivity to regional information, and is non-invasive and non-ionising.
Chronotropic Responses of Human Heart Tissue Cultures
Authors: T. D. CHANG, G. R. CUMMING
Journal: Circulation Research (1972)

Three presumptive cardiac tissues from aborted human embryos which ranged in length from 2 mm to 4 mm and in age from 53 days to 71 days were maintained in culture beating rhythmically for 18-88 days. Medium renewal, temperature increases (from 31° to 38°C), and pH increases (from 6.92 to 7.75) raised the pulsation rate. Excess potassium stopped the pulsation. Sympathomimetic drugs increased the pulsation rate, and this action was blocked by the beta-receptor inhibitor, propranolol, suggesting the presence of functioning beta-receptor sites in the heart cells by the end of the second month of development.
Understanding the adult moralist requires first understanding the child scientist
Authors: Tamar Kushnir, Nadia Chernyak
Journal: Behavioral and Brain Sciences (2010)

Abstract Children learn from people and about people simultaneously; that is, children consider evidentiary qualities of human actions which cross traditional domain boundaries. We propose that Knobe's moral asymmetries are a natural consequence of this learning process: the way “child scientists” gather evidence for causation, intention, and morality through early social experiences.
α-Haemolysin of<i>Escherichia coli</i>in IBD: a potentiator of inflammatory activity in the colon
Authors: Roland Bücker, Emanuel Schulz, Dorothee Günzel, Christian Bojarski, In-Fah M Lee, Lena J John, Stephanie Wiegand, Traute Janßen, Lothar H Wieler, Ulrich Dobrindt, Lothar Beutin, Christa Ewers, Michael Fromm, Britta Siegmund, Hanno Troeger, Jörg-Dieter Schulzke
Journal: Gut (2014)

<h3>Objective</h3> α-Haemolysin (HlyA) influences host cell ionic homeostasis and causes concentration-dependent cell lysis. As a consequence, HlyA-producing <i>Escherichia coli</i> is capable of inducing 'focal leaks' in colon epithelia, through which bacteria and antigens translocate. This study addressed the role of HlyA as a virulence factor in the pathogenesis of colitis according to the 'leaky gut' concept. <h3>Design</h3> To study the action of HlyA in the colon, we performed oral administration of HlyA-expressing <i>E coli</i>-536 and its isogenic α-haemolysin-deficient mutant (HDM) in three mouse models: wild type, interleukin-10 knockout mice (<i>IL-10</i><sup>−/−</sup>) and monoassociated mice. Electrophysiological properties of the colonised colon were characterised in Ussing experiments. Inflammation scores were evaluated and focal leaks in the colon were assessed by confocal laser-scanning microscopy. <i>HlyA</i> quantity in human colon biopsies was measured by quantitative PCR. <h3>Results</h3> All three experimental mouse models infected with HlyA-producing <i>E coli</i>-536 showed an increase in focal leak area compared with HDM. This was associated with a decrease in transepithelial electrical resistance and an increase in macromolecule uptake. As a consequence, inflammatory activity index was increased to a higher degree in inflammation-prone mice. Mucosal samples from human colon were <i>E coli</i> HlyA-positive in 19 of 22 patients with ulcerative colitis, 9 of 9 patients with Crohn9s disease and 9 of 12 healthy controls. Moreover, focal leaks were found together with 10-fold increased levels of HlyA in active ulcerative colitis. <h3>Conclusions</h3> <i>E coli</i> HlyA impairs intestinal barrier function via focal leak induction in the epithelium, thereby intensifying antigen uptake and triggering intestinal inflammation in vulnerable mouse models. Therefore, HlyA-expressing <i>E coli</i> strains should be considered as potential cofactors in the pathogenesis of intestinal inflammation.
An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Authors: M. Degardin, J. Oliveira, L. Geoffrois, F. Rolland, J.P. Armand, Ph. Bastit, J. Chauvergne, P. Fargeot, M. van Glabbeke, M.A. Lentz, P. Tresca, J. Boudillet, P. Fumoleau, P. Cappelaere
Journal: Annals of Oncology (1998)
Glucose-galactose malabsorption: demonstration of specific jejunal brush border membrane defect.
Authors: I W Booth, P B Patel, D Sule, G A Brown, R Buick, K Beyreiss
Journal: Gut (1988)

Jejunal brush border glucose transport was studied in a patient with glucose-galactose malabsorption and in controls, using jejunal brush border membrane vesicles (BBMV) prepared from conventional jejunal biopsies. Whereas BBMV from controls showed a seven-fold enhancement of D-glucose uptake in the presence of an inwardly directed sodium gradient compared with its absence, no such enhancement was seen in the patient9s vesicles. In BBMV from the patient, initial D-glucose uptake under sodium gradient conditions was only 10% of the mean control value. In contrast, sodium/proton exchange in BBMV from the patient was intact. These data provide the first unequivocal evidence that the jejunal brush border membrane is the site of a specific defect in sodium dependent glucose transport in glucose-galactose malabsorption. Measurement of glucose uptake by BBMV may well be the optimal diagnostic technique in this disorder.
Delayed Preconditioning-Mimetic Action of Nitroglycerin in Patients Undergoing Coronary Angioplasty
Authors: Massoud A. Leesar, Marcus F. Stoddard, Buddhadeb Dawn, Venu G. Jasti, Ronald Masden, Roberto Bolli
Journal: Circulation (2001)

Background —Experimental studies suggest that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked pharmacologically. However, to date, no drug has been tested with respect to its ability to elicit a late PC effect in humans. As a consequence, clinical exploitation of the powerful anti-stunning and anti-infarct actions of late PC has been elusive thus far. Methods and Results —A total of 66 patients were randomized to receive a 4-hour intravenous infusion of nitroglycerin (NTG) or normal saline; on the following day, they underwent percutaneous transluminal coronary angioplasty (three 2-minute balloon inflations 5 minutes apart). Measurements of ST-segment shifts (intracoronary and surface ECGs), regional wall motion (quantitative 2D echocardiography), and chest pain score indicated that the infusion of NTG 24 hours before angioplasty rendered the myocardium relatively resistant to ischemia and that the degree of this cardioprotective effect was comparable to that afforded by the ischemia associated with the first balloon inflation in control subjects (early phase of ischemic PC). Collateral flow (estimated from a pressure-derived index) did not differ between control and NTG-pretreated patients, indicating that the enhanced tolerance to ischemia in NTG-pretreated patients cannot be accounted for by baseline differences in collateral function. Conclusions —NTG protects human myocardium against ischemia 24 hours after its administration. To the best of our knowledge, this is the first report that a late PC effect can be recruited pharmacologically in humans. The results suggest that prophylactic administration of nitrates could be a novel approach to the protection of the ischemic myocardium in patients.
Changes in Prostate Cancer Grade on Serial Biopsy in Men Undergoing Active Surveillance
Authors: Sima P. Porten, Jared M. Whitson, Janet E. Cowan, Matthew R. Cooperberg, Katsuto Shinohara, Nannette Perez, Kirsten L. Greene, Maxwell V. Meng, Peter R. Carroll
Journal: Journal of Clinical Oncology (2011)

Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time.Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates.Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy.A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.
Effectiveness of community physiotherapy and enhanced pharmacy review for knee pain in people aged over 55 presenting to primary care: pragmatic randomised trial
Authors: Elaine M Hay, Nadine E Foster, Elaine Thomas, George Peat, Mike Phelan, Hannah E Yates, Alison Blenkinsopp, Julius Sim
Journal: BMJ (2006)

<b>Objectives</b> To evaluate the effectiveness of two primary care strategies for delivering evidence based care to people aged 55 or over with knee pain: enhanced pharmacy review and community physiotherapy. <b>Design</b> Pragmatic multicentre randomised clinical trial. <b>Setting</b> 15 general practices in North Staffordshire. <b>Participants</b> 325 adults aged 55 years or over (mean 68 years) consulting with knee pain; 297 (91%) reached six month follow-up. <b>Interventions</b> Enhanced pharmacy review (pharmacological management in accordance with an algorithm); community physiotherapy (advice about activity and pacing and an individualised exercise programme); control (advice leaflet reinforced by telephone call). <b>Main outcome measure</b> Change in Western Ontario and McMaster Universities osteoarthritis index (WOMAC) at 3, 6, and 12 months. <b>Results</b> Mean baseline WOMAC pain score was 9.1 (SD 3.7), and mean baseline function score was 29.9 (SD 12.8). At three months, the mean reductions in pain scores were 0.41 (SD 2.8) for control, 1.59 (3.2) for pharmacy, and 1.56 (3.4) for physiotherapy; reductions in function scores were 0.80 (8.5), 2.61 (9.8), and 4.79 (10.8). Compared with control, mean differences in change scores for physiotherapy were 1.15 (95% confidence interval 0.2 to 2.1) for pain and 3.99 (1.2 to 6.8) for function; those for pharmacy were 1.18 (0.3 to 2.1) for pain and 1.80 (−0.8 to 4.5) for function. These differences were not sustained to six or 12 months. Significantly fewer participants in the physiotherapy group reported consulting their general practitioner for knee pain in the follow-up period, and use of non-steroidal anti-inflammatory drugs was lower in the physiotherapy and pharmacy groups than in the control group. <b>Conclusions</b> Evidence based care for older adults with knee pain, delivered by primary care physiotherapists and pharmacists, resulted in short term improvements in health outcomes, reduced use of non-steroidal anti-inflammatory drugs, and high patient satisfaction. Physiotherapy seemed to produce a shift in consultation behaviour away from the traditional general practitioner led model of care. <b>Trial registration</b> UK National Research Register N0286046917; Current Controlled Trials ISRCTN55376150.
Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908
Authors: G. Frasci, G. D’Aiuto, P. Comella, M. D’Aiuto, M. Di Bonito, P. Ruffolo, G. Iodice, A. Petrillo, S. Lastoria, P. Oliviero, I. Capasso, M. Montella, C. Siani, M. Santangelo, L. Vizioli, G. Comella
Journal: Annals of Oncology (2009)
Inhalation Toxicity of Brevetoxin 3 in Rats Exposed for Twenty-Two Days
Authors: Janet M. Benson, Fletcher F. Hahn, Thomas H. March, Jacob D. McDonald, Andrea P. Gomez, Mohan J. Sopori, Andrea J. Bourdelais, Jerome Naar, Julia Zaias, Gregory D. Bossart, Daniel G. Baden
Journal: Environmental Health Perspectives (2005)

Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf. This study assessed possible adverse health effects associated with inhalation exposure to brevetoxin 3, one of the major brevetoxins produced by K. brevis and present in aerosols collected along beaches affected by red tide. Male F344 rats were exposed to brevetoxin 3 at 0, 37, and 237 microg/m3 by nose-only inhalation 2 hr/day, 5 days/week for up to 22 exposure days. Estimated deposited brevetoxin 3 doses were 0.9 and 5.8 microg/kg/day for the low- and high-dose groups, respectively. Body weights of the high-dose group were significantly below control values. There were no clinical signs of toxicity. Terminal body weights of both low- and high-dose-group rats were significantly below control values. Minimal alveolar macrophage hyperplasia was observed in three of six and six of six of the low- and high-dose groups, respectively. No histopathologic lesions were observed in the nose, brain, liver, or bone marrow of any group. Reticulocyte numbers in whole blood were significantly increased in the high-dose group, and mean corpuscular volume showed a significant decreasing trend with increasing exposure concentration. Humoral-mediated immunity was suppressed in brevetoxin-exposed rats as indicated by significant reduction in splenic plaque-forming cells in both low- and high-dose-group rats compared with controls. Results indicate that the immune system is the primary target for toxicity in rats after repeated inhalation exposure to relatively high concentrations of brevetoxins.
MRI diagnosis of accessory soleus muscle strain.
Authors: T Featherstone
Journal: British Journal of Sports Medicine (1995)

An accessory soleus muscle is a rare anatomical variant. Clinical awareness of this entity and the appropriate use of magnetic resonance imaging (MRI) can yield a definitive diagnosis in those patients with symptomatic accessory muscles. A case is presented in which the unique sensitivity of MRI in the evaluation of exertional muscle injuries proved useful in the detection of an accessory soleus muscle strain.
Natural Selection in a Bangladeshi Population from the Cholera-Endemic Ganges River Delta
Authors: Elinor K. Karlsson, Jason B. Harris, Shervin Tabrizi, Atiqur Rahman, Ilya Shlyakhter, Nick Patterson, Colm O’Dushlaine, Stephen F. Schaffner, Sameer Gupta, Fahima Chowdhury, Alaullah Sheikh, Ok Sarah Shin, Crystal Ellis, Christine E. Becker, Lynda M. Stuart, Stephen B. Calderwood, Edward T. Ryan, Firdausi Qadri, Pardis C. Sabeti, Regina C. LaRocque
Journal: Science Translational Medicine (2013)

Natural selection in a Bangladeshi population from the cholera-endemic Ganges River Delta has targeted genes associated with cholera resistance and an innate immunity pathway activated by Vibrio cholerae .
Nitrendipine binding in congestive heart failure due to myocardial infarction.
Authors: I M Dixon, S L Lee, N S Dhalla
Journal: Circulation Research (1990)

Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure x heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4, 8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by [3H]nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, [3H]PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)