tbuckley/cabot-search huggingface dataset:
Who should conduct and interpret the neuropsychological assessment in sports-related concussion?
Authors: R J Echemendia, S Herring, J Bailes
Journal: British Journal of Sports Medicine (2009)

Objective: This paper seeks to (i) describe the education and training of clinical neuropsychologists, (ii) discuss the significant differences between test administration and clinical assessment, (iii) outline the complex factors involved in psychometric test theory and test interpretation, and (iv) provide a framework for the role of clinical neuropsychologists in the interpretation and administration of neuropsychological instruments within the sports context. Design: Review of pertinent professional practice, empirical and theoretical literature. Intervention: Pubmed, Medline and Psych Info databases were reviewed. In total, 35 articles and 2 books were reviewed. Results: The decision to return an athlete to play following sports-related brain injury is complex and requires the analysis of several sources of data. The decision is determined by a team physician; ideally within the context of a multidisciplinary team that employs comprehensive concussion surveillance and management, including baseline and post-injury neuropsychological assessment. Neuropsychologists possess the training and skill sets necessary to provide unique expertise in the assessment of cognitive functioning and post-injury neurocognitive and psychological assessment. Conclusions: Baseline neuropsychological testing is a technical procedure that can be conducted by technicians under the supervision/guidance of a neuropsychologist. Post-injury assessment requires advanced neuropsychological expertise that is best provided by a clinical neuropsychologist. Significant international differences exist with respect to the training and availability of clinical neuropsychologists, which require modification of these views on a country by country basis.
Tolerability and efficacy of N-chlorotaurine in comparison with chloramine T for the treatment of chronic leg ulcers with a purulent coating: a randomized phase II study
Authors: M. Nagl, V.A. Nguyen, W. Gottardi, H. Ulmer, R. Hopfl
Journal: British Journal of Dermatology (2003)

Background The well-known active chlorine compound chloramine T (CAT) with broad-spectrum antimicrobial activity is in common therapeutic use for leg ulcers with purulent coatings; however, this treatment is painful. The tolerability of the less aggressive N-chlorotaurine (NCT), an endogenous compound also produced in vivo by stimulated human granulocytes, could be superior. Objectives To assess the tolerability and efficacy of NCT in the cleaning of purulent coatings in chronic leg ulcers in comparison with CAT. Methods In a double-blind, randomized phase IIb clinical study 40 patients were treated for a median of 7 days (range 3–14) with a 1% aqueous solution of either NCT (20 subjects) or CAT (20 subjects) by twice-daily application of dressings soaked in the test solutions. Criteria for evaluation of tolerability were intensity and duration of pain caused by the ulcer therapy and scores of tissue toxicity (necrosis, granulation tissue and re-epithelialization). Therapeutic efficacy was graded as scores of intensity of purulent coating of the ulcers. Results The concentration tolerated in vitro by human epidermoid carcinoma cells was at least 10-fold higher for NCT (0·01%) compared with CAT (0·0001–0·001%). There was significantly less pain caused by NCT compared with CAT (P < 0·05) on days 1 and 4 and a trend for a shorter duration of pain (P = 0·093). The scores of intensity of coating improved without difference in both treatment groups, whereas granulation and re-epithelialization appeared earlier in the NCT group (P < 0·05). Non-quantitative microbiological cultures from ulcer smears revealed persistence of colonization by bacterial species in approximately half of both treatment groups. Conclusions Both active chlorine compounds were helpful in reducing purulent coatings. Because of its lower toxicity and better tolerability, NCT is of advantage in the treatment of leg ulcers.
Could Interferon Still Play a Role in Metastatic Renal Cell Carcinoma? A Randomized Study of Two Schedules of Sorafenib Plus Interferon-Alpha 2a (RAPSODY)
Authors: Sergio Bracarda, Camillo Porta, Corrado Boni, Armando Santoro, Claudia Mucciarini, Antonio Pazzola, Enrico Cortesi, Donatello Gasparro, Roberto Labianca, Francesco Di Costanzo, Alfredo Falcone, Michela Cinquini, Claudia Caserta, Chiara Paglino, Verena De Angelis
Journal: European Urology (2012)
Goodbye and thank you
Authors: Leo van de Putte
Journal: Annals of the Rheumatic Diseases (2008)

The year 1999 was a landmark year for the European league Against Rheumatism (EULAR) and BMJ Publishing Group: the Annals of the Rheumatic Diseases (ARD), the world’s oldest English rheumatology journal, became the official journal of EULAR, from then on being co-owned by both organisations. This marriage has proven to be a success story; the growing importance and influence of EULAR in the field of rheumatology in its broadest sense being mirrored in a very …
Leukotriene Receptor Antagonists as Potential Therapeutic Agents
Authors: D W Snyder, J H Fleisch
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Leukotrienes are a family of bioactive lipids that have a constellation of pharmacologic effects on respiratory, cardiovascular, and gastrointestinal systems. They produce smooth muscle spasm (1, 2), cause myocardial de­ pression (3), increase vascular permeability ( l , 4) enhance mucous produc­ tion (5), decrease mucociliary transport (6), and have the chemotactic prop­ erty to attract leukocytes to a site of cellular injury (7, 8). The overwhelming evidence suggests that leukotriene synthesis and subsequent release in ex­ perimental animals and in humans are associated with certain pathophysiolog­ ical events. Disorders such as asthma, adult respiratory distress syndrome, chronic bronchitis, cystic fibrosis, septic shock, psoriasis, inflammatory bowel disease, and myocardial ischemia have all been reported to be associ­ ated with increased levels of leukotrienes (9-15). Little is known about the physiological role, if any, of these C20 fatty acids but such information appears on the horizon. For example, recent studies have explored participa­ tion of leukotrienes in the fine tuning of the immune system (16). In addition, early evidence suggests a neuromodulatory role of leukotrienes (17, 18) and other lipoxygenase metabolites in the central nervous system. Membrane phospholipids are the major source of arachidonic acid from which prostaglandins, thromboxanes, and leukotrienes are derived (Figure 1). Activation of phospholipase A2, the enzyme that cleaves arachidonic acid from the two position of the phospholipid molecule, occurs as a consequence of anaphylactoid antigen-antibody reactions, by a variety of chemicals, and in response to cell injury. Leukotrienes are formed de novo by action of a
THE MULTIFACETED REGULATION OF INTERLEUKIN-15 EXPRESSION AND THE ROLE OF THIS CYTOKINE IN NK CELL DIFFERENTIATION AND HOST RESPONSE TO INTRACELLULAR PATHOGENS
Authors: T. A. Waldmann, Y. Tagaya
Journal: Annual Review of Immunology (1999)

Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15R beta and gamma c subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15R alpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.
Novel adaptation of a method to assess responsiveness of bronchial segments in vitro
Authors: BE Mc Parland, PR Johnson, CL Armour, JL Black
Journal: European Respiratory Journal (1998)

In vivo agonist delivery to the lungs is characterized by absorption through the mucosal layer followed by access to the smooth muscle. When agonists are applied to perfused bronchial segments, a difference in potency to agonists applied to the serosal (outside) or mucosal (inside) surface can be demonstrated. In order to elucidate this effect in canine bronchial segments, we adapted a method to assess responsiveness of agonists applied to the inside or outside surface of canine bronchial segments. A 2 cm "fluid-tight" length of bronchus was cannulated and mounted in a perfusion chamber. Auxotonic contraction of the bronchus displaced fluid inside the segment up a column and the change in height of fluid within the column (afterload) was measured as a change in hydrostatic pressure (volumetric). We assessed the optimal conditions for measuring bronchial responsiveness to acetylcholine. Neither stretching segments lengthways from 100 to 140% of resting length, nor altering the transmural pressure from 3 to 21 cmH2O had a significant effect on the potency of acetylcholine applied to the outside surface. Both acetylcholine (n=7) and methacholine (n=4) were approximately 10-fold more potent when applied to the outside surface than the inside surface of bronchial segments (p&lt;0.0001). Furthermore, mechanical removal of the epithelium (n=6) led to a 67-fold increase in potency of acetylcholine applied to the inside surface compared with segments with epithelium. The advantages that this system has over previously reported methods include: 1) agonists can be injected at a low flow rate so as to minimize epithelial stress; 2) changes in luminal volume are measured under conditions of no flow; 3) after-load can be varied such that contraction is either practically isotonic or auxotonic; and 4) a "barrier effect" of the epithelium of canine bronchial segments can be demonstrated. This new adapted method will provide us with the means to assess the relationship between in vitro and in vivo responsiveness in human bronchi.
Origins of Human Malaria: Rare Genomic Changes and Full Mitochondrial Genomes Confirm the Relationship of Plasmodium falciparum to Other Mammalian Parasites but Complicate the Origins of Plasmodium vivax
Authors: S. W. Roy, M. Irimia
Journal: Molecular Biology and Evolution (2008)

Despite substantial work, the phylogeny of malaria parasites remains debated. The matter is complicated by concerns about patterns of evolution in potentially strongly selected genes as well as the extreme AT bias of some Plasmodium genomes. Particularly contentious has been the position of the most virulent human parasite Plasmodium falciparum, whether grouped with avian parasites or within a larger clade of mammalian parasites. Here, we study 3 classes of rare genomic changes, as well as the sequences of mitochondrial ribosomal RNA (rRNA) genes. We report 3 lines of support for a clade of mammalian parasites: 1) we find no instances of spliceosomal intron loss in a hypothetical ancestor of P. falciparum and the avian parasite Plasmodium gallinaceum, suggesting against a close relationship between those species; 2) we find 4 genomic mitochondrial indels supporting a mammalian clade, but none grouping P. falciparum with avian parasites; and 3) slowly evolving mitochondrial rRNA sequences support a mammalian parasite clade with 100% posterior probability. We further report a large deletion in the mitochondrial large subunit rRNA gene, which suggests a subclade including both African and Asian parasites within the clade of closely related primate malarias. This contrasts with previous studies that provided strong support for separate Asian and African clades, and reduces certainty about the historical and geographic origins of Plasmodium vivax. Finally, we find a lack of synapomorphic gene losses, suggesting a low rate of ancestral gene loss in Plasmodium.
Local Recurrence or Cardiovascular Disease: Pay Now or Later
Authors: S. H. Giordano, G. N. Hortobagyi
Journal: JNCI Journal of the National Cancer Institute (2007)

treated with radiation had increased risk of contralateral breast cancer, lung cancer, and mortality from cardiac disease (rate ratio = 1.27 , P <.001 ). The increase in non ‐ breast cancer mortality among irradiated patients, particularly the increase in deaths from heart disease, diminished the benefit of radiation on overall survival endpoints. Individual randomized trials and epidemiologic studies have also demonstrated the cardiac toxicity of adjuvant breast radiotherapy ( 2 ‐ 8 ). In a meta-analysis of eight randomized trials, Cuzick et al. ( 6 ) found a 62% increase in cardiac deaths among women who were treated with radiation therapy. However, all the individual studies in the meta-analysis were initiated before 1975 and used radiotherapy techniques that would now be considered suboptimal. Our own study ( 7 ), based on the Surveillance, Epidemiology, and End Results database, indicated that the risk of cardiac death due to radiotherapy has declined since the 1970s, but not enough time has elapsed to get fi rm estimates of the risk for women treated in the 1990s or 2000s, because cardiac toxicity is a late consequence of therapy that does not emerge until at least a decade after completing radiotherapy. The report by Hooning et al. ( 9 ) in this issue of the Journal provides important new information on the cardiac toxicity of radiation therapy. The study focused on a cohort of 4414 women who were at least 10-year survivors of breast cancer and were identifi ed through the Late Effects Breast Cancer Cohort in The Netherlands. The follow-up in this study was remarkably complete, with information available for 96% of all 10-year survivors. In addition, the median follow-up of almost 18 years was impressively long. Given the late emergence of radiation toxicity, the length of follow-up is critically important. The study has some other unique features: it evaluates morbidity as well as mortality, compares toxicity by radiation fi elds, and evaluates the impact of other cardiac risk factors. Several interesting fi ndings emerge from these analyses. First, this study is consistent with a growing body of literature showing that the risk of myocardial infarction due to radiation therapy has declined over time and provides additional good news for our patients ( 7 , 10 ). Thus, although patients who were diagnosed between 1970 and 1979 with radiation to the left chest wall or to right or left internal mammary fi elds had an increased risk of myocardial infarction, overall, the patients who were diagnosed
Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers.
Authors: G Hecht, C Pothoulakis, J T LaMont, J L Madara
Journal: Journal of Clinical Investigation (1988)

Toxin A of Clostridium difficile causes severe inflammatory enterocolitis in man and animals that appears to be mediated in part by acute inflammatory cells that migrate into the toxin A-exposed mucosa. To determine the direct effects of toxin A on intestinal epithelial permeability and structure in the absence of other modulating factors, we used cultured monolayers of a human intestinal epithelial cell line (T84). A toxin A concentration of 7 x 10(-1) micrograms/ml (3 x 10(-9) M) nearly abolished monolayer transepithelial resistance within 6-8 h. This marked permeability defect occurred while the monolayers were still confluent. Dual sodium-mannitol flux studies localized the permeability defect to the intercellular tight junction. Cytotoxicity assays and morphological evaluation using Nomarski optics and electron microscopy failed to demonstrate any evidence of cell damage at the time the maximum resistance response was observed. Fluorescent staining for F actin, however, revealed a marked decrease in fluorescent intensity in toxin-treated monolayers versus controls. These data show that toxin A can directly affect the barrier function of this model intestinal epithelium and initially does so by selectively enhancing tight junction permeability. Furthermore, cytoskeletal structure is markedly altered over the same time course, although the integrity of individual cells is maintained. Because the cytoskeleton of intestinal epithelial cells is known to be capable of regulating tight junction permeability, we speculate that the above effects of toxin A on epithelial barrier function result from alterations of the cytoskeleton.
A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients
Authors: X. Pivot, P. Koralewski, J.L. Hidalgo, A. Chan, A. Gonçalves, G. Schwartsmann, S. Assadourian, J.P. Lotz
Journal: Annals of Oncology (2008)
A New Formulation of Protein Evolutionary Models that Account for Structural Constraints
Authors: Andrew J. Bordner, Hans D. Mittelmann
Journal: Molecular Biology and Evolution (2013)

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site–site correlations that arise from physical interactions between neighboring amino acid sites. This is mainly due to the difficulty in formulating a computationally tractable model since rate matrices can no longer be used. Here, we introduce a general framework, based on factor graphs, for constructing probabilistic models of protein evolution with site interdependence. Conveniently, efficient approximate inference algorithms, such as Belief Propagation, can be used to calculate likelihoods for these models. We fit an amino acid substitution model of this type that accounts for both solvent accessibility and site–site correlations. Comparisons of the new model with rate matrix models and alternative structure-dependent models demonstrate that it better fits the sequence data. We also examine evolution within a family of homohexameric enzymes and find that site–site correlations between most contacting subunits contribute to a higher likelihood. In addition, we show that the new substitution model has a similar mathematical form to the one introduced in Rodrigue et al. (Rodrigue N, Lartillot N, Bryant D, Philippe H. 2005. Site interdependence attributed to tertiary structure in amino acid sequence evolution. Gene 347:207–217), although with different parameter interpretations and values. We also perform a statistical analysis of the effects of amino acids at neighboring sites on substitution probabilities and find a significant perturbation of most probabilities, further supporting the significant role of site–site interactions in protein evolution and motivating the development of new evolutionary models similar to the one described here. Finally, we discuss possible extensions and applications of the new substitution model.
Blood Mercury Levels in US Children and Women of Childbearing Age, 1999-2000
Authors: Susan E. Schober, Thomas H. Sinks, Robert L. Jones, P. Michael Bolger, Margaret McDowell, John Osterloh, E. Spencer Garrett, Richard A. Canady, Charles F. Dillon, Yu Sun, Catherine B. Joseph, Kathryn R. Mahaffey
Journal: JAMA (2003)

Context Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of exposure. The extent of exposure to methylmercury in US women of reproductive age is not known. Objective To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption. Design and Setting The 1999-2000 data from the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Participants In 1999-2000, 1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate). Main Outcome Measure Blood concentration of total mercury. Results Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 µg/L (95% confidence interval [CI], 0.30-0.39 µg/L) in children and 1.02 µg/L (95% CI, 0.85-1.20 µg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 µg/L vs 0.51 µg/L; P &amp;amp;lt;.001). Conclusions Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 µg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.
IAP inhibitors enhance co-stimulation to promote tumor immunity
Authors: Michael Dougan, Stephanie Dougan, Joanna Slisz, Brant Firestone, Matthew Vanneman, Dobrin Draganov, Girija Goyal, Weibo Li, Donna Neuberg, Richard Blumberg, Nir Hacohen, Dale Porter, Leigh Zawel, Glenn Dranoff
Journal: The Journal of Experimental Medicine (2010)

The inhibitor of apoptosis proteins (IAPs) have recently been shown to modulate nuclear factor κB (NF-κB) signaling downstream of tumor necrosis factor (TNF) family receptors, positioning them as essential survival factors in several cancer cell lines, as indicated by the cytotoxic activity of several novel small molecule IAP antagonists. In addition to roles in cancer, increasing evidence suggests that IAPs have an important function in immunity; however, the impact of IAP antagonists on antitumor immune responses is unknown. In this study, we examine the consequences of IAP antagonism on T cell function in vitro and in the context of a tumor vaccine in vivo. We find that IAP antagonists can augment human and mouse T cell responses to physiologically relevant stimuli. The activity of IAP antagonists depends on the activation of NF-κB2 signaling, a mechanism paralleling that responsible for the cytotoxic activity in cancer cells. We further show that IAP antagonists can augment both prophylactic and therapeutic antitumor vaccines in vivo. These findings indicate an important role for the IAPs in regulating T cell-dependent responses and suggest that targeting IAPs using small molecule antagonists may be a strategy for developing novel immunomodulating therapies against cancer.
Protein-Losing Enteropathy Due to T-Cell Large Granular Lymphocyte Leukemia
Authors: Yu-Yan Hwang, Anskar Y.H. Leung, Irene O.L. Ng, Gavin S.W. Chan, Kwok-Wah Chan, Eric Tse, Yok-Lam Kwong
Journal: Journal of Clinical Oncology (2009)