tbuckley/cabot-search huggingface dataset:
Chemoradiation Followed by Surgery Compared With Chemoradiation Alone in Squamous Cancer of the Esophagus: FFCD 9102
Authors: Laurent Bedenne, Pierre Michel, Olivier Bouché, Chantal Milan, Christophe Mariette, Thierry Conroy, Denis Pezet, Bernard Roullet, Jean-François Seitz, Jean-Philippe Herr, Bernard Paillot, Patrick Arveux, Franck Bonnetain, Christine Binquet
Journal: Journal of Clinical Oncology (2007)

Uncontrolled studies suggest that chemoradiation has similar efficacy as surgery for esophageal cancer. Therefore, a randomized trial was carried out to compare, in responders only, chemoradiation alone with chemoradiation followed by surgery in patients with locally advanced tumors.Eligible patients had operable T3N0-1M0 thoracic esophageal cancer. Patients received two cycles of fluorouracil (FU) and cisplatin (days 1 to 5 and 22 to 26) and either conventional (46 Gy in 4.5 weeks) or split-course (15 Gy, days 1 to 5 and 22 to 26) concomitant radiotherapy. Patients with response and no contraindication to either treatment were randomly assigned to surgery (arm A) or continuation of chemoradiation (arm B; three cycles of FU/cisplatin and either conventional [20 Gy] or split-course [15 Gy] radiotherapy). Chemoradiation was considered equivalent to surgery if the difference in 2-year survival rate was less than 10%.Of 444 eligible patients, 259 were randomly assigned; 230 patients (88.8%) had epidermoid cancer, and 29 (11.2%) had glandular carcinoma. Two-year survival rate was 34% in arm A versus 40% in arm B (hazard ratio for arm B v arm A = 0.90; adjusted P = .44). Median survival time was 17.7 months in arm A compared with 19.3 months in arm B. Two-year local control rate was 66.4% in arm A compared with 57.0% in arm B, and stents were less required in the surgery arm (5% in arm A v 32% in arm B; P < .001). The 3-month mortality rate was 9.3% in arm A compared with 0.8% in arm B (P = .002). Cumulative hospital stay was 68 days in arm A compared with 52 days in arm B (P = .02).Our data suggest that, in patients with locally advanced thoracic esophageal cancers, especially epidermoid, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation.
Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women
Authors: Linda R. Peterson, Pilar Herrero, Kenneth B. Schechtman, Susan B. Racette, Alan D. Waggoner, Zulia Kisrieva-Ware, Carmen Dence, Samuel Klein, JoAnn Marsala, Timothy Meyer, Robert J. Gropler
Journal: Circulation (2004)

Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women.We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (MVO2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/MVO2. BMI correlated with MVO2 (r=0.58, P=0.0006), MFAUp (r=0.42, P<0.05), and efficiency (r=-0.40, P<0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r=0.55, P<0.005), MFAU (r=0.62, P<0.001), and MFAO (r=0.58, P<0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MVO2 and efficiency (P=0.0005 and P<0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P<0.05, <0.005, and <0.005, respectively).In young women, obesity is a significant predictor of increased MVO2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.
Latex allergen exposure increases exhaled nitric oxide in symptomatic healthcare workers
Authors: X. Baur, L. Barbinova
Journal: European Respiratory Journal (2005)

The objective of this study was to investigate the clinical and diagnostic impact of baseline exhaled nitric oxide (eNO) levels and latex allergen-induced eNO changes in different healthcare worker groups. Healthcare workers, 31 latex-sensitised and 14 nonsensitised, underwent occupational-type challenge tests with powdered allergenic latex gloves. Sensitised as well as nonsensitised healthcare workers developed a significant eNO increase 1 h after challenge. Conversely, only latex-sensitised employees showed a significant eNO increase 22 h after challenge, which showed a significant relationship with bronchial obstruction (specific airway resistance changes). However, there was no difference in either baseline eNO level or eNO increase after 22 h between asthmatic (n = 13) and rhinitic only (n = 20) responders. The specificity and sensitivity of a 50% eNO increase after 22 h in responders were 100 and 56%, respectively. These results support the assumption that the whole respiratory tract is involved in a combined allergic rhinitis and asthma syndrome. Smoking healthcare workers showed reduced baseline exhaled nitric oxide levels, but, as shown for the first time, an allergen-induced exhaled nitric oxide increase comparable to that of nonsmokers. Corticosteroid therapy inhibited the allergen-induced exhaled nitric oxide change but not the clinical response in the challenge test. These findings suggest that cigarette smoke and corticosteroids initiate distinct molecular mechanisms influencing nitric oxide concentrations in the airways.
Oxidative Regulation of the Na <sup>+</sup> –K <sup>+</sup> Pump in Cardiac Physiology and Pathology
Authors: Gemma A. Figtree, Helge H. Rasmussen, Chia-Chi Liu
Journal: Circulation Research (2013)

1 titled "Redox Signaling in Cardiac Physiology and Pathology" that provides an excellent overview of the expanding number of protein targets in the cardiovascular system undergoing redox regulation by direct posttranslational oxidative modification.The importance of this mode of signaling in both health and disease is well described.We were honored to see the inclusion of our recent work identifying the molecular mechanism for redox regulation of the cardiac Na + -K + pump and hope that this may promote an increased interest in this important membrane protein among cardiovascular researchers.The authors described in detail our work defining glutathionylation of Cys45 of the β 1 subunit of the pump as the mediator of oxidative inhibition, published in Circulation Research in 2009, 2 and the mechanism of stimulation of the Na + -K + pump by NO-dependent reduction in Na + -K + pump glutathionylation. 3The likely contribution of these signaling pathways to cardiac excitation-contraction coupling is highlighted in both the text, and in a helpful figure (Figure 2) 1 .Unfortunately, the only reference that the reader is provided with for this work is an earlier article of ours in which we identified nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase as a key signaling molecule in the inhibition of the cardiac Na + -K + by Angiotensin II. 4 At the time this article was published, we did not know the molecular mechanism by which the inhibition occurred.We feel that omission of the later references may make it difficult for the reader to follow the rationale of our work, in the context of what is otherwise an excellent review.
Dynamic Changes in Myocardial Matrix and Relevance to Disease
Authors: Ai-Hsien Li, Peter P. Liu, Francisco J. Villarreal, Ricardo A. Garcia
Journal: Circulation Research (2014)

The cardiac extracellular matrix (ECM) provides the architectural scaffold to support efficient contraction and relaxation of cardiomyocytes. The elegant design of the ECM facilitates optimal force transduction, electric transmission, intercellular communication, and metabolic exchange within the myocardial microenvironment. In the setting of increased wall stress, injury, or disease, the ECM can undergo a series of dynamic changes that lead to favorable chamber remodeling and functional adaptation. Over time, sustained matrix remodeling can impair diastolic and systolic function caused by excess deposition of interstitial fibrous tissue. These pathological alterations in ECM structure/function are considered central to the evolution of adverse cardiac remodeling and the development of heart failure. This review discusses the complex dynamics of the cardiac ECM in the setting of myocardial infarction, pressure overload, and volume overload. We also summarize the current status of ECM biomarkers that may have clinical value in prognosticating cardiac disease progression in patients. Finally, we discuss the most current status of drugs under evaluation for use in cardiac fibrosis.
Elevated Plasma Levels of Nt-proBNP in Patients With Type 2 Diabetes Without Overt Cardiovascular Disease
Authors: Martin Magnusson, Olle Melander, Bo Israelsson, Anders Grubb, Leif Groop, Stefan Jovinge
Journal: Diabetes Care (2004)

The NH(2)-terminal portion of the precursor of brain natriuretic peptide (Nt-proBNP) has been reported to be elevated in left ventricular dysfunction. This peptide is a split product from the proBNP molecule, and its level in the circulation is not, as the mature BNP peptide, dependent on the peripheral number of BNP receptors. We aimed to test the hypothesis that asymptomatic left ventricular dysfunction (ALVD), as estimated by Nt-proBNP, would be more prevalent in patients with type 2 diabetes without overt cardiovascular disease in comparison with matched control subjects.The study population consisted of 253 patients with type 2 diabetes and 230 matched control subjects aged 40-70 years without any overt heart disease from primary care centers in Western Finland and Southern Sweden. Nt-proBNP was measured in plasma by competitive enzyme immunosorbent assay.Patients with type 2 diabetes were shown to have higher Nt-proBNP values (360.9 pmol/l [262.6-467.9]) than control subjects (302.7 pmol/l [215.4-419.2]) (P < 0.001). Nt-proBNP levels were independently related to diabetes after adjustment for age, sex, systolic and diastolic blood pressure, BMI, heart rate, drug treatment, serum creatinine, and cystatin C.Our data suggest that the secretion of Nt-proBNP is increased in type 2 diabetic patients with no overt heart disease, suggesting that type 2 diabetes is associated with a higher prevalence of ALVD than hitherto thought. Nt-proBNP may thus serve as a screening instrument to select patients with type 2 diabetes who could benefit from an echocardiographical examination.
GP dementia payment scheme will end next year, NHS confirms
Authors: A. O'Dowd
Journal: BMJ (2014)

A controversial scheme that pays GPs to improve their diagnosis rates of dementia cases will not continue after next spring, the NHS has confirmed. Simon Stevens, NHS England chief executive, told Pulse magazine in an interview published on 26 November1 that the scheme had been a “one time catch-up opportunity” and would not be renewed.

The national enhanced service known as the Dementia Identification Scheme,2 launched last month by NHS England, pays GPs £55 for each additional patient on their list with a new diagnosis of dementia. 

From the outset the scheme was intended to run only from October 2014 to March 2015, but …
Protecting the health of the @hlete: how online technology may aid our common goal to prevent injury and illness in sport
Authors: Evert Verhagen, Caroline Bolling
Journal: British Journal of Sports Medicine (2015)

Online technology dominates our era and eHealth has become a reality for sports clinicians and researchers. Contemporary online platforms enable self-monitoring and provide tailored feedback to the different stakeholders who play a role in the health and care of athletes. Innovations such as digital monitoring, mobile applications and connected hardware provide the critical tools to solve current enigmas in sports medicine research, and to streamline and facilitate injury prevention, management and rehabilitation. eHealth is not an emerging future of sports medicine—the technology to move our field forward in terms of research and practice is already available. This Analysis is based on Evert Verhagen's keynote presentation at the IOC World Conference on Injury and Illness Prevention in Sport (Monaco, 12 April 2014). It outlines the use of eHealth in research, implementation and practice, and provides an overview of possibilities and opportunities that existing and emerging eHealth solutions provide for sports and exercise medicine and physiotherapy.
Optogenetic activation of Gq signalling modulates pacemaker activity of cardiomyocytes
Authors: Thomas Beiert, Tobias Bruegmann, Philipp Sasse
Journal: Cardiovascular Research (2014)

Investigation of Gq signalling with pharmacological agonists of Gq-coupled receptors lacks spatio-temporal precision. The aim of this study was to establish melanopsin, a light-sensitive Gq-coupled receptor, as a new tool for the investigation of spatial and temporal effects of Gq stimulation on pacemaking in cardiomyocytes at an early developmental stage. A vector for ubiquitous expression of melanopsin was tested in HEK293FT cells, which showed light-induced production of inositol-1,4,5-trisphosphate and elevation of intracellular Ca2+ concentration. Mouse embryonic stem cells were stably transfected with this plasmid and differentiated into spontaneously beating embryoid bodies (EBs). Cardiomyocytes within EBs showed melanopsin expression and illumination (60 s, 308.5 nW/mm2, 470 nm) of EBs increased beating rate within 10.2 ± 1.7 s to 317.1 ± 16.3% of baseline frequency. Illumination as short as 5 s was sufficient for generating the maximal frequency response. After termination of illumination, baseline frequency was reached with a decay constant of 27.1 ± 2.5 s. The light-induced acceleration of beating frequency showed a sigmoid dependence on light intensity with a half maximal effective light intensity of 41.7 nW/mm2. Interestingly, EBs showed a high rate of irregular contractions after termination of high-intensity illumination. Local Gq activation by illumination of a small region in a functional syncytium of cardiomyocytes led to pacemaker activity within the illuminated area. Light-induced Gq activation in melanopsin-expressing cardiomyocytes increases beating rate and generates local pacemaker activity. We propose that melanopsin is a powerful optogenetic tool for the investigation of spatial and temporal aspects of Gq signalling in cardiovascular research.
Response to a Novel Multitargeted Tyrosine Kinase Inhibitor Pazopanib in Metastatic Merkel Cell Carcinoma
Authors: Matthew Davids, Amanda Charlton, Swee-Siang Ng, Mei-Ling Chong, Kevin Laubscher, Mohammed Dar, Jeffrey Hodge, Richie Soong, Boon Cher Goh
Journal: Journal of Clinical Oncology (2009)
Prognosis of Mild Cognitive Impairment in Early Parkinson Disease
Authors: Kenn Freddy Pedersen, Jan Petter Larsen, Ole-Bjorn Tysnes, Guido Alves
Journal: JAMA Neurology (2013)

Mild cognitive impairment (MCI) is common in Parkinson disease (PD), but the prognostic value of MCI in early PD is unknown.To examine the course of MCI and its progression to dementia in an incident PD cohort.Prospective longitudinal cohort study.The Norwegian ParkWest study, an ongoing population-based study of the incidence, neurobiology, and prognosis of PD in western and southern Norway.A population-based cohort of 182 patients with incident PD monitored for 3 years.Serial neuropsychological tests of attention, executive function, verbal memory, and visuospatial skills were administered at baseline, 1 year, and 3 years. Patients were classified as having MCI and received a diagnosis of dementia according to published consensus criteria.Significantly more patients with MCI than without MCI at baseline (10 of 37 [27.0%] vs 1 of 145 [0.7%]; relative risk, 39.2 [95% CI, 5.2-296.5]; P < .001) progressed to dementia during follow-up. Of those with MCI at baseline, 8 of 37 (21.6%) had MCI that reverted to normal cognition during follow-up. Mild cognitive impairment at the 1-year visit was associated with a similar progression rate to dementia (10 of 36 patients [27.8%]) and reversion rate to normal cognition (7 of 36 [19.4%]). However, among the 22 patients with persistent MCI at baseline and the 1-year visit, 10 (45.5%) developed dementia and only 2 (9.1%) had MCI that reverted to normal cognition by the end of study.Mild cognitive impairment at PD diagnosis predicts a highly increased risk for early dementia. Repeated neuropsychological testing increases the prognostic accuracy of MCI with respect to early dementia development in PD.
Brain 'imaging' in the Renaissance
Authors: A. Paluzzi, A. Belli, P. Bain, L. Viva
Journal: Journal of the Royal Society of Medicine (2007)

During the Renaissance, a period of 'rebirth' for humanities and science, new knowledge and speculation began to emerge about the function of the human body, replacing ancient religious and philosophical dogma. The brain must have been a fascinating mystery to a Renaissance artist, but some speculation existed at that time on the function of its parts. Here we show how revived interest in anatomy and life sciences may have influenced the figurative work of Italian and Flemish masters, such as Rafael, Michelangelo and David. We present a historical perspective on the artists and the period in which they lived, their fascination for human anatomy and its symbolic use in their art. Prior to the 16th century, knowledge of the brain was limited and influenced in a dogmatic way by the teachings of Galen(1) who, as we now know, conducted his anatomical studies not on humans but on animals.(2) Nemesus, Bishop of Emesa, in around the year 400 was one of the first to attribute mental faculties to the brain, specifically to the ventricles. He identified two anterior (lateral) ventricles, to which he assigned perception, a middle ventricle responsible for cognition and a posterior ventricle for memory.(2,3) After a long period of stasis in the Middle Ages, Renaissance scholars realized the importance of making direct observations on dissected cadavers. Between 1504 and 1507, Leonardo da Vinci conducted experiments to reveal the anatomy of the ventricular system in the brain. He injected hot wax through a tube thrust into the ventricular cavities of an ox and then scraped the overlying brain off, thus obtaining, in a simple but ingenious way, an accurate cast of the ventricles.(2,4) Leonardo shared the belief promoted by scholarly Christians that the ventricles were the abode of rational soul. We have several examples of hidden symbolism in Renaissance paintings, but the influence of phrenology and this rudimentary knowledge of neuroanatomy on artists of that period is under-recognized. In the absence of documentary or scientific evidence as to the real intentions of these painters, the notion of such commixture of sacred and profane remains speculative and probably controversial, but at the same time fascinating and provocative. Here we present three examples of Renaissance masterpieces where such symbolism may have been used, although probably many more exist. Conducting an artistic, philosophical and anatomical analysis of the paintings can be an intriguing exercise, but the interpretation will inevitably be conjectural.
Carotid arterial stiffness, elastic fibre network and vasoreactivity in semicarbazide-sensitive amine-oxidase null mouse
Authors: N MERCIER, M OSBORNEPELLEGRIN, K ELHADRI, A KAKOU, C LABAT, L LOUFRANI, D HENRION, P CHALLANDE, S JALKANEN, B FEVE
Journal: Cardiovascular Research (2006)

Objective: We examined the arterial phenotype of semicarbazide-sensitive amine-oxidase null mouse (SSAO −/−) using various techniques including high resolution echotracking.
Relationship between inflammation and joint destruction in early rheumatoid arthritis: a mathematical description
Authors: M C Wick
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> The relationship between inflammation and joint destruction in rheumatoid arthritis (RA) has not been unequivocally characterised. Joint destruction may result from the cumulative inflammatory burden over time, modified by an individual constant factor. <b>Objective:</b> To test the hypothesis that the relationship between radiological progression and inflammation can mathematically be expressed as: where ℜ is a factor that varies from person to person. <b>Methods:</b> Clinical data and radiographs of 76 patients with early RA receiving different disease modifying antirheumatic drugs were analysed. Radiographs were quantified using the modified Larsen score and the "<i>X-Ray RheumaCoach</i>" software. The cumulative inflammatory burden was estimated by the time integrated 28 joint Disease Activity Score (DAS28), calculated as the area under the curve. <b>Results:</b> 76 patients with early RA who started treatment with methotrexate (n = 20), sulfasalazine (n = 37), or oral gold (n = 19) monotherapy were evaluated. The mean (SEM) DAS28 decreased from 4.6 (0.1) at baseline to 2.3 (0.1) after 2 years. The mean (SEM) ΔLarsen score from baseline to year 2 was 10.3 (1.5). Correlation between cumulative inflammation and radiographic change was poor. In contrast, when calculating a person's factor ℜ in year 1 (ℜ1) and year 2 (ℜ2), a strong and significant correlation (<i>r</i> = 0.58, p&lt;0.000001) was seen between ℜ1 and ℜ2. <b>Conclusions:</b> Joint destruction is the result of the cumulative burden of inflammation over time, modified by an individual factor ℜ that remains relatively constant over the first 2 years of observation. The data support a mathematical model that expresses the interrelationship between inflammation and joint destruction.