tbuckley/cabot-search huggingface dataset:
The single nucleotide polymorphism <scp><i>CRTh2</i></scp> rs533116 is associated with allergic asthma and increased expression of <scp>CRT</scp>h2
Authors: E. Campos Alberto, E. MacLean, C. Davidson, N. S. Palikhe, J. Storie, C. Tse, D. Brenner, I. Mayers, H. Vliagoftis, A. El‐Sohemy, L. Cameron
Journal: Allergy (2012)

Abstract Background CRT h2 (chemoattractant‐receptor homologous molecule expressed on T h2 cells) is expressed by T h2 cells and other cells involved in allergic inflammation. Single nucleotide polymorphisms ( SNP s) in CRTh2 (rs11571288, rs545659, rs634681) have been associated with various phenotypes of allergy in ethnically distinct populations. Here, we assessed the association between CRTh2 rs533116 and allergic asthma, expression of CRT h2 and T h2 cytokine production. Methods CRTh2 rs533116 was genotyped in an ethnically diverse population ( n = 1282). The proportion of cells expressing CRT h2 was determined in peripheral blood from subjects with allergic airways disease and controls as well as with in vitro differentiated T h2 cells. Receptor function was assessed by stimulating T h2 cells with the CRT h2‐specific agonist 13,14‐dihydro‐15‐keto‐ PGD 2 ( DK ‐ PGD 2 ) and measuring IL ‐4 and IL ‐13 by intracellular staining and ELISA . Results CRTh2 rs533116 was associated with allergic asthma in White people (2.67 [1.09–6.55], P &lt; 0.05), and expression of CRT h2 was higher in subjects with allergic airways disease compared to controls ( P &lt; 0.05). Among allergic individuals, the AA genotype was significantly associated with more eosinophils and higher expression of CRT h2 by both CD 4 + T cells and eosinophils ( P &lt; 0.05). In vitro , the AA genotype was associated with a higher proportion of CRT h2 + cells during T h2 differentiation as well as more IL ‐4 and IL ‐13 expression following DK ‐ PGD 2 stimulation ( P &lt; 0.05). Conclusions These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRT h2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.
Necrotizing Cutaneous Mucormycosis after a Tornado in Joplin, Missouri, in 2011
Authors: Robyn Neblett Fanfair, Kaitlin Benedict, John Bos, Sarah D. Bennett, Yi-Chun Lo, Tolu Adebanjo, Kizee Etienne, Eszter Deak, Gordana Derado, Wun-Ju Shieh, Clifton Drew, Sherif Zaki, David Sugerman, Lalitha Gade, Elizabeth H. Thompson, Deanna A. Sutton, David M. Engelthaler, James M. Schupp, Mary E. Brandt, Julie R. Harris, Shawn R. Lockhart, George Turabelidze, Benjamin J. Park
Journal: New England Journal of Medicine (2012)

Mucormycosis is a fungal infection caused by environmentally acquired molds. We investigated a cluster of cases of cutaneous mucormycosis among persons injured during the May 22, 2011, tornado in Joplin, Missouri.We defined a case as a soft-tissue infection in a person injured during the tornado, with evidence of a mucormycete on culture or immunohistochemical testing plus DNA sequencing. We conducted a case-control study by reviewing medical records and conducting interviews with case patients and hospitalized controls. DNA sequencing and whole-genome sequencing were performed on clinical specimens to identify species and assess strain-level differences, respectively.A total of 13 case patients were identified, 5 of whom (38%) died. The patients had a median of 5 wounds (range, 1 to 7); 11 patients (85%) had at least one fracture, 9 (69%) had blunt trauma, and 5 (38%) had penetrating trauma. All case patients had been located in the zone that sustained the most severe damage during the tornado. On multivariate analysis, infection was associated with penetrating trauma (adjusted odds ratio for case patients vs. controls, 8.8; 95% confidence interval [CI], 1.1 to 69.2) and an increased number of wounds (adjusted odds ratio, 2.0 for each additional wound; 95% CI, 1.2 to 3.2). Sequencing of the D1-D2 region of the 28S ribosomal DNA yielded Apophysomyces trapeziformis in all 13 case patients. Whole-genome sequencing showed that the apophysomyces isolates were four separate strains.We report a cluster of cases of cutaneous mucormycosis among Joplin tornado survivors that were associated with substantial morbidity and mortality. Increased awareness of fungi as a cause of necrotizing soft-tissue infections after a natural disaster is warranted.
Regional Variations in Diagnostic Practices
Authors: Yunjie Song, Jonathan Skinner, Julie Bynum, Jason Sutherland, John E. Wennberg, Elliott S. Fisher
Journal: New England Journal of Medicine (2010)

Current methods of risk adjustment rely on diagnoses recorded in clinical and administrative records. Differences among providers in diagnostic practices could lead to bias.We used Medicare claims data from 1999 through 2006 to measure trends in diagnostic practices for Medicare beneficiaries. Regions were grouped into five quintiles according to the intensity of hospital and physician services that beneficiaries in the region received. We compared trends with respect to diagnoses, laboratory testing, imaging, and the assignment of Hierarchical Condition Categories (HCCs) among beneficiaries who moved to regions with a higher or lower intensity of practice.Beneficiaries within each quintile who moved during the study period to regions with a higher or lower intensity of practice had similar numbers of diagnoses and similar HCC risk scores (as derived from HCC coding algorithms) before their move. The number of diagnoses and the HCC measures increased as the cohort aged, but they increased to a greater extent among beneficiaries who moved to regions with a higher intensity of practice than among those who moved to regions with the same or lower intensity of practice. For example, among beneficiaries who lived initially in regions in the lowest quintile, there was a greater increase in the average number of diagnoses among those who moved to regions in a higher quintile than among those who moved to regions within the lowest quintile (increase of 100.8%; 95% confidence interval [CI], 89.6 to 112.1; vs. increase of 61.7%; 95% CI, 55.8 to 67.4). Moving to each higher quintile of intensity was associated with an additional 5.9% increase (95% CI, 5.2 to 6.7) in HCC scores, and results were similar with respect to laboratory testing and imaging.Substantial differences in diagnostic practices that are unlikely to be related to patient characteristics are observed across U.S. regions. The use of clinical or claims-based diagnoses in risk adjustment may introduce important biases in comparative-effectiveness studies, public reporting, and payment reforms.
Emergency care networks
Authors: K George M M Alberti
Journal: BMJ (2004)

such, often struggle to meet the medical, nursing, and social care needs of dying people and their families.These changes will greatly affect care for dying people and may increase the number of hospital admissions.However, one important initiative is gaining momentum within primary care.The Gold Standards Framework is a resource for organising proactive palliative care in the community and is supported by funding from the Cancer Services Collaborative, Macmillan Cancer Relief, and the National Lottery. 10 The framework provides a detailed guide to providing holistic, patient centred care and thereby facilitates effective care in the community.Other recently initiated mechanisms for developing primary palliative care include the training of general practitioners with a special interest in palliative care and the new end of life initiative in England to improve palliative care provision by generalists and to share examples of good practice.To support such developments it is essential that primary palliative care is supported by an adequate academic base. 11This is admittedly a challenging arena in which to undertake research, but progress has been made in recent years in developing conceptual models and research architectures for studying end of life issues.Now we need to build on this work to ensure that the understanding and insights gleaned can be translated into effective interventions.Every person with a progressive illness has a right to palliative care. 12Patients desire a reassuring professional presence in the face of death.General practitioners and community nurses are trusted by patients and are in a position to provide effective, equitable, and accessible palliative care.This will happen only if they have adequate time and resources and work in a system that encourages such care.Patients who receive holistic support in the community may be less likely to require expensive admission to hospital and often futile treatments at the end of their lives.
The epidemiology of ice hockey injuries.
Authors: U Jørgensen, S Schmidt-Olsen
Journal: British Journal of Sports Medicine (1986)

As part of the injury profylaxes in Denmark a questionnaire investigation was undertaken in 14 randomly chosen ice hockey teams--out of 266 players, 210 answered (79%). The injury incidence per player per 1000 hours was 4.7, i.e. 1.5 in training and 38.0 in match. Half of the injuries were localised to the head (28%) and lower extremities (27%), 19% to the upper extremities and 7% to the back. Of these 48% were contusions. Knee and elbow injuries were of longest duration. The necessity for increased shock absorption in helmets and barriers as well as built-in rotational and collateral stabilizers in the existing knee protectors for injury prophylaxis is stressed.
Predictive testing for BRCA1 and 2 mutations: a male contribution
Authors: P.A. Daly, C. Nolan, A. Green, W. Ormiston, N. Cody, T. McDevitt, B. O’hIci, D. Byrne, E. McDermott, D.N. Carney, N. O’Higgins, D.E. Barton
Journal: Annals of Oncology (2003)
Shed Membrane Microparticles With Procoagulant Potential in Human Atherosclerotic Plaques
Authors: Ziad Mallat, Bénédicte Hugel, Jeanny Ohan, Guy Lesèche, Jean-Marie Freyssinet, Alain Tedgui
Journal: Circulation (1999)

Background —The specific role of apoptosis in human atherosclerosis remains unknown. During apoptotic cell death, phosphatidylserine exposure on the cell surface confers a high tissue-factor (TF)–dependent procoagulant activity. Methods and Results —In this study, we examined the role of apoptotic cell death in the promotion of plaque thrombogenicity. TF expression and its relation to apoptosis was analyzed in 16 human atherosclerotic plaques by the use of immunohistochemical techniques. The presence of shed membrane apoptotic microparticles was analyzed in extracts from 6 human atherosclerotic plaques and 3 underlying arterial walls. The microparticles were captured by annexin V and their amounts estimated with respect to their phospholipid content by use of a prothrombinase assay. The prothrombogenic potential of the microparticles was further assessed by the measurement of total and microparticle-dependent TF activity in the extracts. The cell origin of the microparticles was determined after capture by specific antibodies. We were able to detect marked TF expression in the plaques in close proximity to apoptotic cells and debris, suggesting a potential interaction between TF and the apoptotic cell surfaces. High levels of shed membrane apoptotic microparticles were detected in extracts from atherosclerotic plaques but not in the underlying arterial walls (29.5±3.7 nmol/L phosphatidylserine equivalent versus 1.3±0.4 nmol/L, respectively, P &lt;0.02). The microparticles were mainly of monocytic and lymphocytic origin and retained 97±2% of total TF activity, indicating a direct causal relationship between shed membrane microparticles and procoagulant activity of plaque extracts. Conclusions —These results indicate that shed membrane microparticles with procoagulant potential are produced in human atherosclerotic plaques. Apoptosis could be a critical determinant of plaque thrombogenicity after plaque rupture.
The use of a new breath-actuated inhaler by patients with severe airflow obstruction
Authors: RJ Fergusson, J Lenney, GJ McHardy, GK Crompton
Journal: European Respiratory Journal (1991)

The ability of patients with severe airflow limitation (forced expiratory volume in one second less than 1.0 l or peak expiratory flow rate less than 200 l.min.1) to use a new breath-actuated inhaler (BAI) was assessed. One hundred and fifty six patients attending two respiratory units entered and completed the study. Subjects were instructed how to use the device and after attempting to trigger the BAI had flow-volume loops measured. One hundred and fifty one (97%) were able to actuate the inhaler on their first (146) or second (5) attempt. The five unsuccessful patients did not have the most severe airways obstruction. It is concluded that this new device, which is actuated at low inspiratory flow rates, can be used by patients with severe airflow limitation and represents an important advance in inhaler technology.
Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells.
Authors: D K Dunn-Walters, P G Isaacson, J Spencer
Journal: The Journal of Experimental Medicine (1995)

The splenic marginal zone (MGZ), which surrounds the mantle zone (MTZ) in human splenic white pulp, contains a phenotypically and morphologically distinct population of B cells. The origin of MGZ B cells is uncertain. Whereas some experiments in rodents have suggested that they are a distinct cell lineage responsible for the immune response to T-independent type 2 antigens, others have suggested that they are memory B cells derived from a germinal center (GC) response. The progeny of a GC reaction is expected to have rearranged immunoglobulin (Ig) genes that are mutated. The distribution of mutations would be expected to reflect the selection of Ig by its affinity for antigen. We have analyzed rearranged Ig heavy chain variable region (VH) 6 and VH 4.21 genes in MGZ and MTZ B cells microdissected from frozen sections of human spleen to determine whether these genes have the properties of an affinity-selected memory B cell population. MTZ B cells contained germline Ig VH genes, confirming previous reports and providing an internal control for mutational analysis. MGZ B cells contained Ig VH genes that were mutated, showing that these cells had been subjected to a mutational mechanism characteristically active in the GC. The rearranged VH 6 genes showed patterns of mutation indicative of an antigen selection process, whereas the distribution of mutations in VH 4.21 genes was not characteristic of gene selection by conventional T-dependent antigen. Our studies provide the first evidence that the human splenic MGZ is a reservoir of memory B cells.
Soft Tissue Sarcoma or Malignant Mesenchymal Tumors in the First Year of Life: Experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee
Authors: D. Orbach, A. Rey, O. Oberlin, J. Sanchez de Toledo, M.J. Terrier-Lacombe, A. van Unnik, E. Quintana, M.C.G. Stevens
Journal: Journal of Clinical Oncology (2005)

Purpose To describe the outcome of infants with a histologically confirmed diagnosis of malignant mesenchymal tumor (MMT) included in the International Society of Paediatric Oncology studies MMT 84 and MMT 89. Patients and Methods One hundred two infants (≤ 12 months old) were included. Twenty-four children were less than 3 months old, and 16 were less than 1 month old. Sixty-four patients had rhabdomyosarcoma (RMS), 26 had undifferentiated sarcoma, and 12 had other histology. Clinical TNM stage was stage I (41%), II (39%), III (6%), and IV (14%). First-line treatment was ifosfamide, vincristine, dactinomycin, whereas the second-line combination consisted of either cisplatin and doxorubicin (in MMT 84) or vincristine, carboplatin, etoposide/teniposide (in MMT 89). Chemotherapy doses were adapted to age. Local therapy was conservative surgery as often as possible. Results After a median follow-up of 7.8 years (range, 0.1 to 13 years), 5-year overall survival (OS) and event-free survival rates were 66% and 55% for the total study population and 72% and 60% for nonmetastatic patients, respectively. Only two of 13 stage IV patients survived. Sixty-seven percent of newborn infants survived. Infants with alveolar subtype had a poorer survival than those with non-RMS MMT or nonalveolar RMS (5-year OS, 37% v 75% or 82%, respectively; P = .002). When compared with older children with MMT, young age does not seem to be an important prognostic factor. Conclusion OS was satisfactory even when local treatment was not aggressive, although the prognosis was poor for infants with alveolar RMS or metastatic tumors. Chemotherapy toxicity was manageable with appropriate dose modification.
Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses.
Authors: D J Berg, M W Leach, R Kühn, K Rajewsky, W Müller, N J Davidson, D Rennick
Journal: The Journal of Experimental Medicine (1995)

We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in the regulation of inflammatory and immune reactions in the skin. In these experiments, irritant and contact hypersensitivity (CH) responses were elicited in mice with targeted disruptions of the IL-4 (IL-4T) or IL-10 (IL-10T) gene. Our study showed that IL-4T and wild-type (wt) mice exhibited equivalent responses to the irritant croton oil. In contrast, the response of IL-10T mice challenged with croton oil was abnormally increased. When IL-10T mice were exposed to a higher dose of irritant, irreversible tissue damage occurred. By comparison, any treatment of wt mice with croton oil resulted in far less tissue damage and resolution of inflammation. Neutralizing antibody studies demonstrated that the necrosis that occurred in IL-10T mice was due to the overproduction of tumor necrosis factor. The anti-tumor necrosis factor antibody treatment of IL-10T mice did not significantly reduce the edema or the influx of inflammatory cells, suggesting that these changes were due to the uncontrolled production of other proinflammatory cytokines. T cell-dependent immune responses were also evaluated using the contact sensitizer oxazolone. The response of IL-4T mice did not differ from wt mice. In contrast, IL-10T mice mounted an exaggerated CH response, increased in both magnitude and duration as compared with wt mice. Based on these studies, we have concluded that IL-10, but not IL-4, is a natural suppressant of irritant responses and of CH, and it limits immunopathologic damage in the skin.
Pain and pain tolerance in professional ballet dancers.
Authors: B Tajet-Foxell, F D Rose
Journal: British Journal of Sports Medicine (1995)

Pain experience in sport had been the subject of increasing research in recent years. While sports professionals have generally been found to have higher pain thresholds than control subjects the reasons for this are not entirely clear. The present study seeks to investigate one possible explanatory factor, the importance of the popular image of the physical activity and of the self-image of its participants, by examining pain experience in professional ballet dancers. Like sports professionals, dancers were found to have higher pain and pain tolerance thresholds than age matched controls in the Cold Pressor Test. However, they also reported a more acute experience of the sensory aspects of the pain. Explanations of this apparent paradox are discussed both in terms of the neuroticism scores of the two groups and in terms of the dancers' greater experience of pain and its relationship with physical activity. The results illustrated the importance of using multidimensional measures of pain in this type of investigation.
Urinary Placental Growth Factor and Preeclampsia—Reply
Journal: JAMA (2005)

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Oxidative changes and signalling pathways are pivotal in initiating age-related changes in articular cartilage
Authors: Wang Hui, David A Young, Andrew D Rowan, Xin Xu, Tim E Cawston, Carole J Proctor
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To use a computational approach to investigate the cellular and extracellular matrix changes that occur with age in the knee joints of mice. <h3>Methods</h3> Knee joints from an inbred C57/BL1/6 (ICRFa) mouse colony were harvested at 3–30 months of age. Sections were stained with H&amp;E, Safranin-O, Picro-sirius red and antibodies to matrix metalloproteinase-13 (MMP-13), nitrotyrosine, LC-3B, Bcl-2, and cleaved type II collagen used for immunohistochemistry. Based on this and other data from the literature, a computer simulation model was built using the Systems Biology Markup Language using an iterative approach of data analysis and modelling. Individual parameters were subsequently altered to assess their effect on the model. <h3>Results</h3> A progressive loss of cartilage matrix occurred with age. Nitrotyrosine, MMP-13 and activin receptor-like kinase-1 (ALK1) staining in cartilage increased with age with a concomitant decrease in LC-3B and Bcl-2. Stochastic simulations from the computational model showed a good agreement with these data, once transforming growth factor-β signalling via ALK1/ALK5 receptors was included. Oxidative stress and the interleukin 1 pathway were identified as key factors in driving the cartilage breakdown associated with ageing. <h3>Conclusions</h3> A progressive loss of cartilage matrix and cellularity occurs with age. This is accompanied with increased levels of oxidative stress, apoptosis and MMP-13 and a decrease in chondrocyte autophagy. These changes explain the marked predisposition of joints to develop osteoarthritis with age. Computational modelling provides useful insights into the underlying mechanisms involved in age-related changes in musculoskeletal tissues.