tbuckley/cabot-search huggingface dataset:
Accuracy of distinguishing between dysembryoplastic neuroepithelial tumors and other epileptogenic brain neoplasms with [11C]methionine PET
Authors: S. Rheims, S. Rubi, S. Bouvard, E. Bernard, N. Streichenberger, M. Guenot, D. Le Bars, A. Hammers, P. Ryvlin
Journal: Neuro-Oncology (2014)

Dysembryoplastic neuroepithelial tumors (DNTs) represent a prevalent cause of epileptogenic brain tumors, the natural evolution of which is much more benign than that of most gliomas. Previous studies have suggested that [(11)C]methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumors, and hence optimize the management of patients. Here, we reassessed the diagnostic accuracy of MET-PET for the differentiation between DNT and other epileptogenic brain neoplasms in a larger population.We conducted a retrospective study of 77 patients with focal epilepsy related to a nonrapidly progressing brain tumor on MRI who underwent MET-PET, including 52 with a definite histopathology. MET-PET data were assessed by a structured visual analysis that distinguished normal, moderately abnormal, and markedly abnormal tumor methionine uptake and by semiquantitative ratio measurements.Pathology showed 21 DNTs (40%), 10 gangliogliomas (19%), 19 low-grade gliomas (37%), and 2 high-grade gliomas (4%). MET-PET visual findings significantly differed among the various tumor types (P < .001), as confirmed by semiquantitative analyses (P < .001 for all calculated ratios), regardless of gadolinium enhancement on MRI. All gliomas and gangliogliomas were associated with moderately or markedly increased tumor methionine uptake, whereas 9/21 DNTs had normal methionine uptake. Receiver operating characteristics analysis of the semiquantitative ratios showed an optimal cutoff threshold that distinguished DNTs from other tumor types with 90% specificity and 89% sensitivity.Normal MET-PET findings in patients with an epileptogenic nonrapidly progressing brain tumor are highly suggestive of DNT, whereas a markedly increased tumor methionine uptake makes this diagnosis unlikely.
Recurrent pulmonary thromboembolism presenting with cardiac arrhythmias.
Authors: A K Brown, P Newton, E A Hamilton, V Anderson
Journal: Thorax (1979)

Pulmonary emboli seldom recur, and when recurrence does occur it is not associated with permanent sequelae unless there is progressive pulmonary arterial hypertension. Five patients with clinical and perfusion lung scan evidence of recurrent pulmonary embolism presented with abnormal cardiac rhythms without evidence of progressive pulmonary hypertension. Twenty-four-hour ambulatory electrocardiographic monitoring was valuable in diagnosis and in assessing the effectiveness of treatment. Although palpitation was the main complaint, other symptoms included tiredness, mild exertional dyspnoea, and chest discomfort unrelated to effort. Symptomatic improvement coincided with objective evidence of improvement from repeat lung scans and 24-hour ECG records. Antiarrhythmic agents controlled the arrhythmias but were subsequently withdrawn without the return of symptoms. Four of the five patients continued to take anticoagulants for two years. We believe that these five patients represent a group of patients with recurrent pulmonary emboli and a recognisable clinical picture dominated by arrhythmias unrelated to progressive pulmonary arterial hypertension. Long-term anticoagulant treatment was associated with clinical improvement.
Authors’ 2015 additions to the IOC consensus statement: Relative Energy Deficiency in Sport (RED-S)
Authors: Margo Mountjoy, Jorunn Sundgot-Borgen, Louise Burke, Susan Carter, Naama Constantini, Constance Lebrun, Nanna Meyer, Roberta Sherman, Kathrin Steffen, Richard Budgett, Arne Ljungqvist
Journal: British Journal of Sports Medicine (2015)

Albert Einstein said: "The important thing is to never stop questioning."A group of 11 IOC authors have called attention, as others in the past, 3 4 to a problem that is wider and more complex than originally identified when the term 'Female Athlete Triad' (Triad or FAT) was first coined in 1992.Just as knowledge evolves, so too should ideas and constructs on how to address it.Given the evolution of science since 1992, and to more accurately describe the clinical syndrome originally known as the Female Athlete Triad, the IOC introduced a more comprehensive, broader term: Relative Energy Deficiency in Sport.The syndrome of RED-S refers to impaired physiological functioning caused by relative energy deficiency, and includes but is not limited to impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular health.
Torture and doctors' dual obligation
Authors: J. Sheather, R. Beynon, T. Davies, K. Abbasi
Journal: BMJ (2015)

People held in detention are vulnerable. Complex physical and psychological health needs are compounded by loss of freedom that constrains detainees’ ability to assert their interests. The purpose of custodial institutions and environments is not therapeutic. Health professionals who look after detainees find themselves torn by divided loyalties: their primary obligation to patient wellbeing conflicts with their obligations to institutions and employers. Involvement of health professionals in torture is indisputable. A recent report by the US Senate Intelligence Select Committee confirmed that the line between medical care and interrogation was breached by the Central Intelligence Agency (CIA) during the “war on terror.” Health professionals supervised waterboarding sessions and cleared detainees for enhanced interrogation. Medical staff were involved in rectal feeding and hydration, which the CIA considered useful in overcoming detainees’ refusal of food and fluids despite no evidence of its benefit. Meanwhile in Saudi Arabia, a panel of .... Language: en
NUTRITION OF THE HOST AND NATURAL RESISTANCE TO INFECTION
Authors: Howard A. Schneider, Norton D. Zinder
Journal: The Journal of Experimental Medicine (1956)

The double strain inoculation test as used for the assay of nutritional factors capable of enhancing survivorship in mouse salmonellosis has been modified and improved. The modification has been based on the use of genetically marked strains of S. typhimurium, and substitutes for survivorship a bacteriological datum, a certain minimum population size of the virulent salmonellae in the mouse spleen at a certain time. The analysis permitting this substitution and the economies achieved by the modification has been presented. In the course of development of the new assay evidence was obtained that the nutrient entity or entities responsible for enhanced survivorship, as measured by the bacteriological correlate, are not stored in the mouse. A deficiency state was achieved 24 hours after supplying the basal synthetic diet. Similarly, positive effect of active nutrients was evident as soon as 24 hours after feeding.
A novel antigen-processing-defective phenotype in major histocompatibility complex class II-positive CIITA transfectants is corrected by interferon-gamma.
Authors: C A Siegrist, E Martinez-Soria, I Kern, B Mach
Journal: The Journal of Experimental Medicine (1995)

Presentation of exogenous protein antigens to T lymphocytes is based on the intersection of two complex pathways: (a) synthesis, assembly, and transport of major histocompatibility complex (MHC) class II-invariant chain complexes from the endoplasmic reticulum to a specialized endosomal compartment, and (b) endocytosis, denaturation, and proteolysis of antigens followed by loading of antigenic peptides onto newly synthesized MHC class II molecules. It is believed that expression of MHC class II heterodimers, invariant chain and human leukocyte antigen-DM is both necessary and sufficient to reconstitute a functional MHC class II loading compartment in antigen-presenting cells. Expression of each of these essential molecules is under the control of the MHC class II transactivator CIITA. Unexpectedly, however, whereas interferon gamma stimulation does confer effective antigen-processing function to nonprofessional antigen presenting cells, such as melanoma cells, expression of the CIITA transactivator alone is not sufficient. Activation of antigen-specific T cells thus requires additional CIITA-independent factor(s), and such factor(s) can be induced by interferon gamma.
Positive Correlation Between Evolutionary Rate and Recombination Rate in Drosophila Genes with Male-Biased Expression
Authors: Zhi Zhang, John Parsch
Journal: Molecular Biology and Evolution (2005)

Previous studies have shown that genes that are expressed predominantly or exclusively in males tend to evolve rapidly in comparison to other genes. In most cases, however, it is unknown whether this rapid evolution is the result of increased positive (or sexual) selection on male-expressed traits or if it is due to a relaxation of selective constraints. To distinguish between these two possibilities, we analyzed the relationship between the nonsynonymous substitution rate (dN) and local recombination rate for 343 Drosophila genes that were classified as male, female, or nonsex biased in their expression. For the male-biased genes, a positive correlation between dN and recombination rate was observed. This can be explained by an increased rate of adaptive evolution in regions of higher recombination due to a reduction of Hill-Robertson interference. In contrast, the correlation between dN and recombination rate was negative for both female- and nonsex-biased genes, suggesting that these genes are primarily subject to purifying selection, which is expected to be less effective in regions of reduced recombination.
Clusterin Decreases Oxidative Stress in Lung Fibroblasts Exposed to Cigarette Smoke
Authors: Stefano Carnevali, Fabrizio Luppi, Domenico D'Arca, Andrea Caporali, Maria Paola Ruggieri, Maria Vittoria Vettori, Andrea Caglieri, Serenella Astancolle, Francesca Panico, Pierpaola Davalli, Antonio Mutti, Leonardo M. Fabbri, Arnaldo Corti
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Cigarette smoke causes injury to lung fibroblasts, partly by means of oxidative stress, and oxidative stress can lead to various lung diseases, such as chronic obstructive pulmonary disease. Clusterin is a widely distributed protein with many functions, including cellular protection in response to oxidative stress.Objectives: To determine whether clusterin is involved in the defense of the lung against cigarette smoke, we investigated the effects of cigarette smoke extract on clusterin expression and its protective effect, if any, against oxidative stress.Methods: Fibroblasts were coincubated with conditioned medium and cigarette smoke extract, and bronchial biopsy specimens obtained from nonsmokers, smokers, and ex-smokers were analyzed by immunohistochemistry.Measurements and Main Results: At concentrations of 2.5 and 5.0%, cigarette smoke extract induced oxidative stress. It also markedly increased the expression of two clusterin isoforms (60 and 76–80 kD) and the 76–80-kD isoform was secreted in the incubation medium. Coincubation of fibroblasts with conditioned medium significantly decreased the cellular oxidation caused by the cigarette smoke extract. Immunohistochemical analysis of clusterin on bronchial biopsy specimens obtained from smokers and ex-smokers showed localization of clusterin mainly in the submucosa.Conclusions: We conclude that clusterin may have a protective effect against cigarette smoke–induced oxidative stress in lung fibroblasts.
Functional Expression of Mutations in the Human NaCl Cotransporter
Authors: Joke C. de Jong, Walter A. van der Vliet, Lambertus P. W. J. van den Heuvel, Peter H. G. M. Willems, Nine V. A. M. Knoers, René J. M. Bindels
Journal: Journal of the American Society of Nephrology (2002)

Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. This disorder results from mutations in the thiazide-sensitive NaCl cotransporter (NCC). To elucidate the functional implications of mutations associated with this disorder, metolazone-sensitive (22)Na(+) uptake, subcellular localization, and glycosidase-sensitive glycosylation of human NCC (hNCC) were determined in Xenopus laevis oocytes expressing FLAG-tagged wild-type or mutant hNCC. Injection of 10 ng of FLAG-tagged hNCC cRNA resulted in metolazone-sensitive (22)Na(+) uptake of 3.4 +/- 0.2 nmol Na(+)/oocyte per 2 h. Immunocytochemical analysis revealed sharp immunopositive staining at the plasma membrane. In agreement with this finding, a broad endoglycosidase H-insensitive band of 130 to 140 kD was present in Western blots of total membranes. The plasma membrane localization of this complex-glycosylated protein was confirmed by immunoblotting of purified plasma membranes. The mutants could be divided into two distinct classes. Class I mutants (G439S, T649R, and G741R) exhibited no significant metolazone-sensitive (22)Na(+) uptake. Immunopositive staining was present in a diffuse band just below the plasma membrane. This endoplasmic reticulum and/or pre-Golgi complex localization was further suggested by the complete absence of the endoglycosidase H-insensitive band. Class II mutants (L215P, F536L, R955Q, G980R, and C985Y) demonstrated significant metolazone-sensitive (22)Na(+) uptake, although uptake was significantly lower than that obtained with wild-type hNCC. The latter mutants could be detected at and below the oocyte plasma membrane, and immunoblotting revealed the characteristic complex-glycosylated bands. In conclusion, this study substantiates NCC processing defects as the underlying pathogenic mechanism in Gitelman's syndrome.
Role of inflammation in nocturnal asthma.
Authors: T W Mackay, W A Wallace, S E Howie, P H Brown, A P Greening, M K Church, N J Douglas
Journal: Thorax (1994)

BACKGROUND--Nocturnal airway narrowing is a common problem for patients with asthma but the role of inflammation in its pathogenesis is unclear. Overnight changes in airway inflammatory cell populations were studied in patients with nocturnal asthma and in control normal subjects. METHODS--Bronchoscopies were performed at 0400 hours and 1600 hours in eight healthy subjects and in 10 patients with nocturnal asthma (&gt; 15% overnight fall in peak flow plus at least one awakening/week with asthma). The two bronchoscopies were separated by at least five days, and both the order of bronchoscopies and site of bronchoalveolar lavage (middle lobe or lingula with contralateral lower lobe bronchial biopsy) were randomised. RESULTS--In the normal subjects there was no difference in cell numbers and differential cell counts in bronchoalveolar lavage fluid between 0400 and 1600 hours, but in the nocturnal asthmatic subjects both eosinophil counts (median 0.11 x 10(5) cells/ml at 0400 hours, 0.05 x 10(5) cells/ml at 1600 hours) and lymphocyte numbers (0.06 x 10(5) cells/ml at 0400 hours, 0.03 x 10(5) cells/ml at 1600 hours) increased at 0400 hours, along with an increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid (3.0 micrograms/ml at 0400 hours, 2.0 micrograms/l at 1600 hours). There were no changes in cell populations in the bronchial biopsies or in alveolar macrophage production of hydrogen peroxide, GM-CSF, or TNF alpha in either normal or asthmatic subjects at 0400 and 1600 hours. There was no correlation between changes in overnight airway function and changes in cell populations in the bronchoalveolar lavage fluid. CONCLUSIONS--This study confirms that there are increases in inflammatory cell populations in the airway fluid at night in asthmatic but not in normal subjects. The results have also shown a nocturnal increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid, but these findings do not prove that these inflammatory changes cause nocturnal airway narrowing.
Proceedings: Penicillamine or gold for rheumatoid arthritis? Multicentre trial using 'blind' observers. The first six months.
Authors: E C Huskisson, T J Gibson, H W Balme, H Berry, H C Burry, R Grahame, F D Hart, D R Henderson, J A Wojtulewski
Journal: Annals of the Rheumatic Diseases (1974)
1,25 Dihydroxyvitamin D Amplifies Type A Natriuretic Peptide Receptor Expression and Activity in Target Cells
Authors: Songcang Chen, Xi-Ping Ni, Michael H Humphreys, David G Gardner
Journal: Journal of the American Society of Nephrology (2004)

1,25 dihydroxyvitamin D (VD) has been shown to exert a number of beneficial effects on cardiovascular function, including reduction in BP and inhibition of cardiac hypertrophy. In an effort to identify a possible mechanistic link between VD and these salutary effects, the role of VD in controlling the activity and expression of the type A natriuretic peptide receptor (NPR-A), a receptor that signals reductions in BP and suppression of cellular growth in the myocardium and vascular wall, was investigated. VD, as well as the nonhypercalcemic analogue RO-25-6760, increased NPR-A–dependent cyclic guanosine monophosphate production and NPR-A gene expression in cultured rat aortic smooth muscle cells. The increase in NPR-A expression was associated with an increase in NPR-A gene promoter activity that was critically dependent on the presence of a functional VD receptor response element located approximately 495 bp upstream from the transcription start site of the gene. This element was associated with the VD receptor/retinoid X receptor complex <i>in vitro</i>. Mutation of this element resulted in complete elimination of the VD-dependent induction of the NPR-A gene promoter but did not affect osmotic stimulation of the promoter. Treatment of rats with RO-25-6760 for 7 d increased the atrial natriuretic peptide–dependent excretion of sodium and cyclic guanosine monophosphate without affecting mean arterial BP or plasma calcium levels. This was associated with a twofold increase in NPR-A mRNA levels in the inner medulla. Amplification of NPR-A activity represents a plausible mechanism to account for at least some of the beneficial effects that VD exerts on cardiovascular function.
Quality of reporting in systematic reviews of adverse events: systematic review
Authors: L. Zorzela, S. Golder, Y. Liu, K. Pilkington, L. Hartling, A. Joffe, Y. Loke, S. Vohra
Journal: BMJ (2014)

<b>Objectives </b>To examine the quality of reporting of harms in systematic reviews, and to determine the need for a reporting guideline specific for reviews of harms. <b>Design</b> Systematic review. <b>Data sources</b> Cochrane Database of Systematic Reviews (CDSR) and Database of Abstracts of Reviews of Effects (DARE). <b>Review methods</b> Databases were searched for systematic reviews having an adverse event as the main outcome, published from January 2008 to April 2011. Adverse events included an adverse reaction, harms, or complications associated with any healthcare intervention. Articles with a primary aim to investigate the complete safety profile of an intervention were also included. We developed a list of 37 items to measure the quality of reporting on harms in each review; data were collected as dichotomous outcomes (“yes” or “no” for each item). <b>Results</b> Of 4644 reviews identified, 309 were systematic reviews or meta-analyses primarily assessing harms (13 from CDSR; 296 from DARE). Despite a short time interval, the comparison between the years of 2008 and 2010-11 showed no difference on the quality of reporting over time (P=0.079). Titles in fewer than half the reviews (proportion of reviews 0.46 (95% confidence interval 0.40 to 0.52)) did not mention any harm related terms. Almost one third of DARE reviews (0.26 (0.22 to 0.31)) did not clearly define the adverse events reviewed, nor did they specify the study designs selected for inclusion in their methods section. Almost half of reviews (n=170) did not consider patient risk factors or length of follow-up when reviewing harms of an intervention. Of 67 reviews of complications related to surgery or other procedures, only four (0.05 (0.01 to 0.14)) reported professional qualifications of the individuals involved. The overall, unweighted, proportion of reviews with good reporting was 0.56 (0.55 to 0.57); corresponding proportions were 0.55 (0.53 to 0.57) in 2008, 0.55 (0.54 to 0.57) in 2009, and 0.57 (0.55 to 0.58) in 2010-11. <b>Conclusion</b> Systematic reviews compound the poor reporting of harms data in primary studies by failing to report on harms or doing so inadequately. Improving reporting of adverse events in systematic reviews is an important step towards a balanced assessment of an intervention.
TCT-509 Impact On Outcome Of Different Types Of Carotid Stents: Results From The European Registry Of Carotid Artery Stenting.
Authors: Eugenio Stabile, Pallav Garg, Alberto Cremonesi, Marc Bosiers, Bernhard Reimers, Carlo Setacci, Piergiorgio Cao, Andrej Schmidt, Horst Sievert, Patrick Peeters, Dimitrios Nikas, Martin Werner, Gianmarco de Donato, Giambattista Parlani, fausto Castriota, Marius Hornung, Laura Mauri, Giuseppe Giugliano, Giovanni Esposito, Paolo Rubino
Journal: Journal of the American College of Cardiology (2013)
Liver-specific ablation of Krüppel-associated box-associated protein 1 in mice leads to male-predominant hepatosteatosis and development of liver adenoma
Authors: Karolina Bojkowska, Fabio Aloisio, Marco Cassano, Adamandia Kapopoulou, Francesca Santoni de Sio, Nadine Zangger, Sandra Offner, Cristina Cartoni, Charles Thomas, Simon Quenneville, Kai Johnsson, Didier Trono
Journal: Hepatology (2012)

The liver is characterized by sexually dimorphic gene expression translating into sex-specific differences in lipid, drug, steroid hormone, and xenobiotic metabolism, with distinct responses of males and females to environmental challenges. Here, we investigated the role of the Krüppel-associated box (KRAB)-associated protein 1 (KAP1) epigenetic regulator in this process. Liver-specific KAP1 knockout (KO) led to strikingly sexually dimorphic phenotypic disturbances, including male-predominant steatosis and hepatic tumors with up-regulation of protein kinase B and extracellular signal-related kinases 1/2 mitogen-activated protein kinase signaling. This correlated with the sex-specific transcriptional dysregulation of a wide range of metabolic genes, notably those involved in retinol and sex hormone processing as well as in detoxification. Furthermore, chromatin immunoprecipitation followed by deep sequencing indicated that a number of dysregulated genes are direct targets of the KRAB/KAP1 repression system. Those genes include sexually dimorphic cytochrome P 450 Cyp2d9, glutathione S-transferase π, Cyp2a, Cyp2b, and Cyp3a gene clusters. Additionally, we identified a male-restricted KAP1-binding site in the fat-specific protein 27 gene, correlating with its male-predominant up-regulation upon Kap1 deletion, suggesting that the latter might be an important trigger in the development of male-specific hepatosteatosis and secondary tumorigenesis. Conclusion: This work reveals KRAB/KAP1-mediated transcriptional regulation as a central event in metabolic control hormones, drugs, and xenobiotics in the liver and further links disturbances in these processes with hepatic carcinogenesis. (HEPATOLOGY 2012)