tbuckley/cabot-search huggingface dataset:
The impact of a delay in intensive care unit admission for community-acquired pneumonia
Authors: J. Phua, W.J. Ngerng, T.K. Lim
Journal: European Respiratory Journal (2010)

The primary objective of the present study was to evaluate the effect on hospital mortality of a delay in intensive care unit (ICU) admission for severe community-acquired pneumonia (CAP). The secondary objectives were to assess if such delays were associated with treatment variations by the emergency department (ED) and deterioration in the general wards, and to evaluate the prognostic ability of the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) minor criteria. We retrospectively compared patients who were admitted straight from the ED to the ICU (direct group, n = 54) and those who were first admitted from the ED to the general wards before ICU transfer (delayed group, n = 49), over 2.5 yrs. Even after excluding patients who required mechanical ventilation and/or vasopressors at the ED, delayed ICU admission was an independent predictor of hospital mortality (OR 9.61). The delayed group received fewer fluid boluses in the ED and rapidly deteriorated in the general wards. The presence of ≥3 IDSA/ATS minor criteria was associated with increased mortality in the delayed group. In conclusion, prompt recognition of severe CAP using the IDSA/ATS minor criteria, followed by aggressive management at the ED and direct ICU admission, are all crucial toward improving outcomes.
Five‐year follow‐up on the PAT study: specific immunotherapy and long‐term prevention of asthma in children
Authors: B. Niggemann, L. Jacobsen, S. Dreborg, H. A. Ferdousi, S. Halken, A. Høst, A. Koivikko, D. Koller, L. A. Norberg, R. Urbanek, E. Valovirta, U. Wahn, C. Möller
Journal: Allergy (2006)

Background: A 3‐year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long‐term preventive effect, we performed a follow up – 2 years after termination of immunotherapy. Methods: A total of 183 children, aged 6–14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment. Conjunctival provocation tests (CPTs) and methacholine bronchial provocation tests were carried out during the season and winter after 5 years. The development of asthma was assessed by clinical evaluation. Results: The significant improvement in hay fever and CPT results observed after 3 years of SIT persisted at the 5‐year follow‐up. No difference in bronchial responsiveness to methacholine was found after 5 years because of spontaneous improvement during the follow‐up period in the control patients. The immunotherapy‐treated children had significantly less asthma after 5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3–5.7)] in favor of SIT for prevention of development of asthma and significantly less patients reported an increase in asthma scores ( P &lt; 0.01). Conclusion: Immunotherapy for 3 years with standardized allergen extracts of grass and/or birch shows long‐term clinical effect and preventive effect on development of asthma in children with seasonal rhinoconjunctivitis.
Anticomplement receptor activity in the serum of patients with primary biliary cirrhosis.
Authors: G Y Minuk, J Vergalla, R G Hanson, J H Hoofnagle, M M Frank, E A Jones
Journal: Gut (1986)

Patients with primary biliary cirrhosis have a defect in the receptor mediated clearance of complement coated erythrocytes by fixed macrophages of the reticuloendothelial system. To investigate the probable mechanism of this defect peripheral blood monocytes were isolated from nine patients with primary biliary cirrhosis and seven control subjects and the ability of these cells to form rosettes with complement coated, IgM-sensitised sheep erythrocytes was assessed. Primary biliary cirrhosis peripheral blood monocytes formed rosettes to the same extent as control peripheral blood monocytes (71.0 +/- 7.1% [SEM] versus 73.3 +/- 4.3%) suggesting normal complement receptor function of primary biliary cirrhosis peripheral blood monocytes. When primary biliary cirrhosis or control peripheral blood monocytes were preincubated with primary biliary cirrhosis serum, however, the per cent of peripheral blood monocytes that formed rosettes was decreased: 2.4 +/- 0.8 and 3.1 +/- 1.3 fold respectively. To study this phenomenon further, fractions containing IgG or IgM synthesised by cultures of control or primary biliary cirrhosis lymphocytes were prepared. Rosette formation was not affected by exposure to fractions containing control or primary biliary cirrhosis IgG or control IgM, but was markedly inhibited (6.0 +/- 4.8 fold) by exposure to fractions containing primary biliary cirrhosis IgM. Similar results were obtained when freshly isolated peripheral blood monocytes or peripheral blood monocytes that had been cultured for 7-10 days--that is, macrophages, were used. Assuming that one can draw inferences concerning the status of fixed macrophages from data obtained using peripheral blood monocytes, the results of this study suggest that the complement specific defect in reticuloendothelial system clearance function in primary biliary cirrhosis is not caused by abnormality in the functional status of complement receptors on fixed macrophages but rather by a factor present in the serum of patients with primary biliary cirrhosis that has the capacity to inhibit the adherence of complement coated erythrocytes to complement receptors present on the surface of fixed macrophages. This serum factor does not appear to be a complement component but rather a product of peripheral blood mononuclear cells, other than IgG.
Effectiveness of the pneumococcal polysaccharide vaccine in preventing pneumonia in the elderly
Authors: A. Domínguez, C. Izquierdo, L. Salleras, L. Ruiz, D. Sousa, J-M. Bayas, M. Nebot, W. Varona, J-M. Celorrio, J. Carratalà
Journal: European Respiratory Journal (2010)

The objective of our study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV) in preventing hospital admission for community-acquired pneumonia (CAP) in people ≥65 yrs of age. We conducted a matched case–control study in patients with CAP admitted to five Spanish hospitals. Cases were persons aged ≥65 yrs admitted to hospital through the emergency department, who presented a clinical and radiological pattern compatible with pneumonia, assessed using established criteria. We matched each case with three control subjects by sex, age (±5 yrs), date of hospitalisation (±30 days) and underlying disease. The study period was May 1, 2005 to January 31, 2007. The PPV immunisation status of cases and controls was investigated. Adjusted ORs for vaccination were calculated using logistic regression analysis. A total of 489 cases and 1,467 controls were included in the final analysis. The overall adjusted vaccination effectiveness for all patients was 23.6% (95% CI 0.9–41.0). The adjusted vaccination effectiveness for immunosuppressed patients was 21.0% (95% CI -18.7–47.5). Our results suggest that the PPV may potentially reduce hospitalisations for pneumonia in the elderly and supports vaccination programmes in this age group.
Epidemiology of injuries in the Australian Football League, seasons 1997–2000
Authors: J Orchard, H Seward
Journal: British Journal of Sports Medicine (2002)

To describe the epidemiology of injuries in the Australian Football League (AFL) over four seasons.An injury was defined as "any physical or medical condition that caused a player to miss a match in the regular season." The rationale for this definition was to eliminate a previously noted tendency of team recorders to interpret injury definitions subjectively. Administrative records of injury payments to players who did not play matches determined the occurrence of an injury.The seasonal incidence of new injuries was 39 per club (of 40 players) per season (of 22 matches). The match injury incidence for AFL games was 25.7 injuries per 1000 player hours. The injury prevalence (percentage of players missing through injury in an average week) was 16%. The recurrence rate of injuries was 17%. The most common and prevalent injury was hamstring strain (six injuries per club per season, resulting in 21 missed matches per club per season), followed in prevalence by anterior cruciate ligament and groin injuries.The injury definition of this study does not produce incidence rates that are complete for all minor injuries. However, the determination of an injury is made by a single entity in exactly the same manner for all teams, which overcomes a significant methodological flaw present in other multiteam injury surveillance systems.
Enhancement of human eosinophil-mediated killing of Schistosoma mansoni larvae by mononuclear cell products in vitro.
Authors: M C Veith, A E Butterworth
Journal: The Journal of Experimental Medicine (1983)

Previous studies have shown that eosinophils from eosinophilic individuals differ functionally from those of normal individuals. In order to test whether agents that might induce eosinophilia could also affect eosinophil function, we have compared the capacity of culture supernatants from mononuclear cells of eosinophilic or normal individuals to enhance eosinophil activity, as reflected by an increased killing of schistosomula of Schistosoma mansoni in vitro. An enhancing activity was detected, which increased both the antibody-dependent, and to some extent the antibody-independent killing of schistosomula by eosinophils, in the absence of complement. Under similar conditions, the supernatants failed to stimulate an otherwise undetectable neutrophil-mediated killing. The activity could be removed from the assay by washing, without reversing previous eosinophil stimulation, and was not directly toxic to the schistosomula. Preliminary characterization of the activity indicated that it was relatively heat-stable at 100 degrees C for 30 min, and had an estimated molecular weight of 35,000-45,000 as judged by G-200 Sephadex fractionation. The activity was produced by a nonlymphocytic, nonspecific esterase-containing adherent mononuclear cell in the absence of either Con A or antigenic stimulation. Significant enhancing activity was detectable after 1 h of culture and continued for at least 25 h. Protein synthesis was required for its production or release. Although the activity was detectable in supernatants from both eosinophilic and normal individuals, the supernatants that demonstrated highest activity and that could be titrated out furthest were generally derived from eosinophilic individuals, suggesting that there might be some association between eosinophilia and enhanced eosinophil function.
Familial and Genetic Effects on Motor Coordination, Laterality, and Reading-Related Cognition
Authors: Clyde Francks, Simon E. Fisher, Angela J. Marlow, I. Laurence MacPhie, Kathleen E. Taylor, Alex J. Richardson, John F. Stein, Anthony P. Monaco
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Recent research has provided evidence for a genetically mediated association between language or reading-related cognitive deficits and impaired motor coordination. Other studies have identified relationships between lateralization of hand skill and cognitive abilities. With a large sample, the authors aimed to investigate genetic relationships between measures of reading-related cognition, hand motor skill, and hand skill lateralization. METHOD: The authors applied univariate and bivariate correlation and familiality analyses to a range of measures. They also performed genomewide linkage analysis of hand motor skill in a subgroup of 195 sibling pairs. RESULTS: Hand motor skill was significantly familial (maximum heritability=41%), as were reading-related measures. Hand motor skill was weakly but significantly correlated with reading-related measures, such as nonword reading and irregular word reading. However, these correlations were not significantly familial in nature, and the authors did not observe linkage of hand motor skill to any chromosomal regions implicated in susceptibility to dyslexia. Lateralization of hand skill was not correlated with reading or cognitive ability. CONCLUSIONS: The authors confirmed a relationship between lower motor ability and poor reading performance. However, the genetic effects on motor skill and reading ability appeared to be largely or wholly distinct, suggesting that the correlation between these traits may have arisen from environmental influences. Finally, the authors found no evidence that reading disability and/or low general cognitive ability were associated with ambidexterity.
Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish
Authors: Bensheng Ju, Jan Spitsbergen, Christopher J Eden, Michael R Taylor, Wenbiao Chen
Journal: Molecular Cancer (2009)

Abstract The zebrafish has become an important model for cancer research. Several cancer models have been established by transgenic expression of human or mouse oncogenes in zebrafish. Since it is amenable to efficient transgenesis, zebrafish have immense potential to be used for studying interaction of oncogenes and pathways at the organismal level. Using the Gal4VP16-UAS binary transgenic expression approach, we established stable transgenic lines expressing an EGFP fusion protein of an activated zebrafish Smoothened (Smoa1-EGFP). Expression of the zebrafish Smoa1-EGFP itself did not lead to tumor formation either in founder fish or subsequent generations, however, co-expressing a constitutively active human AKT1 resulted in several tumor types, including spindle cell sarcoma, rhabdomyoma, ocular melanoma, astrocytoma, and myoxma. All tumor types showed GFP expression and increased Patched 1 levels, suggesting involvement of zebrafish Smoa1 in tumorigenesis. Immunofluorescence studies showed that tumors also expressed elevated levels of phosphorylated AKT, indicating activation of the PI3K-AKT pathway. These results suggest that co-activation of the hedgehog and AKT pathways promote tumorigenesis, and that the binary transgenic approach is a useful tool for studying interaction of oncogenes and oncogenic pathways in zebrafish.
Molecular subtyping of gastric MALT lymphomas: implications for prognosis and management
Authors: M-Q Du
Journal: Gut (2006)

ince mucosa associated lymphoid tissue (MALT) lymphomas were first recognised as a distinct entity in 1983, their characterisation and management have seen a series of rapid advances.Here we concentrate on MALT lymphomas at the commonest site-the stomach.Historically, despite their indolence, ''localised'' gastric low grade lymphomas were treated with surgery, and chemotherapy or radiotherapy were reserved for systemic spread.This emphasis has gradually changed but the major advance came with the discovery that these tumours were caused by Helicobacter pylori infection, and the remarkable finding that most resolved with its treatment. 1H pylori eradication quickly became a firstline therapy, and the research focus changed to how best to assess which cases would respond to this.Endoscopic ultrasound became important for staging and, to some extent, stage predicted response to H pylori eradication.However, the most exciting research over the past eight years has been in understanding the molecular genetics of these fascinating tumours.In this review, we describe these advances and discuss their implications for management, particularly the extent to which they predict the biological behaviour and response of the tumour to H pylori treatment.www.gutjnl.com
A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing
Authors: Nira R. Pollock, Jason P. Rolland, Shailendra Kumar, Patrick D. Beattie, Sidhartha Jain, Farzad Noubary, Vicki L. Wong, Rebecca A. Pohlmann, Una S. Ryan, George M. Whitesides
Journal: Science Translational Medicine (2012)

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout "bins" [<3× upper limit of normal (ULN), 3 to 5× ULN, and >5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.
<i>O</i> -GlcNAc Signaling in the Cardiovascular System
Authors: Gladys A. Ngoh, Heberty T. Facundo, Ayesha Zafir, Steven P. Jones
Journal: Circulation Research (2010)

Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the beta-O-linkage of N-acetylglucosamine (ie, O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiological and pathological functions. This review introduces readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this review, we focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (eg, hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc-mediated cardioprotection, we discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is and that its roles in the acute and chronic disease settings appear distinct.
Hepatocellular adenomas: Accuracy of magnetic resonance imaging and liver biopsy in subtype classification
Authors: Maxime Ronot, Stephane Bahrami, Julien Calderaro, Dominique-Charles Valla, Pierre Bedossa, Jacques Belghti, Valérie Vilgrain, Valérie Paradis
Journal: Hepatology (2011)

Hepatocellular adenomas (HCAs) are divided into genotype/phenotype subgroups associated with different evolutive profiles. Therefore, recognition of subtype is of clinical importance in patient management. Magnetic resonance imaging (MRI) is considered the most informative imaging modality and liver biopsy a key diagnostic tool whose role in HCA subtyping has never been extensively studied. The purpose of our study was to evaluate the diagnostic performance of MRI and liver biopsy with and without immunohistochemistry and to assess the interobserver agreement for MR classification in a consecutive series of resected HCAs. Forty-seven HCAs with preoperative MRI and biopsy were retrospectively included. MRI data were reviewed independently by two abdominal radiologists blind to the pathological results and classification. Subtyping of HCAs on liver biopsy was made blindly to clinical, biological, and imaging data and to final classification. Routine histological analysis was based on morphological criteria and immunohistochemistry was systematically performed when enough tissue was available. Final subtyping of HCA was based on the examination of the surgical specimen. Radiologists correctly classified HCAs in 85%. The interobserver kappa correlation coefficient was 0.86. Routine histological analysis led to 76.6% of correct classification and 81.6% when immunophenotypical characteristics were available. The additional value of immunophenotypical markers is best in HCAs containing steatosis. Agreement between MRI findings and routine histological analysis was observed in 74.5%, leading to a likelihood ratio of subtype diagnosis higher than 20. MRI and biopsy analysis are two efficient methods in subtyping HCAs and their association increases the diagnosis confidence. Interobserver variability in MRI criteria is very low.
Physiological adaptations to soccer specific endurance training in professional youth soccer players
Authors: K McMillan, J Helgerud, R Macdonald, J Hoff
Journal: British Journal of Sports Medicine (2005)

Improved oxygen uptake improves soccer performance as regards distance covered, involvements with the ball, and number of sprints. Large improvements in oxygen uptake have been shown using interval running. A similar physiological load arising from interval running could be obtained using the soccer ball in training.The main aim was to study physiological adaptations to a 10 week high intensity aerobic interval training program performed by professional youth soccer players, using a soccer specific ball dribbling track.Eleven youth soccer players with a mean (SD) age of 16.9 (0.4) years performed high intensity aerobic interval training sessions twice per week for 10 weeks in addition to normal soccer training. The specific aerobic training consisted of four sets of 4 min work periods dribbling a soccer ball around a specially designed track at 90-95% of maximal heart frequency, with a 3 min recovery jog at 70% of maximal heart frequency between intervals.Mean VO2max improved significantly from 63.4 (5.6) to 69.8 (6.6) ml kg(-1) min(-1), or 183.3 (13.2) to 201.5 (16.2) ml kg(-0.75) min(-1) (p<0.001). Squat jump and counter movement jump height increased significantly from 37.7 (6.2) to 40.3 (6.1) cm and 52.0 (4.0) to 53.4 (4.2) cm, respectively (p<0.05). No significant changes in body mass, running economy, rate of force development, or 10 m sprint times occurred.Performing high intensity 4 min intervals dribbling a soccer ball around a specially designed track together with regular soccer training is effective for improving the VO2max of soccer players, with no negative interference effects on strength, jumping ability, and sprinting performance.