tbuckley/cabot-search huggingface dataset:
Use of strontium ranelate and risk of acute coronary syndrome: cohort study
Authors: Henrik Svanström, Björn Pasternak, Anders Hviid
Journal: Annals of the Rheumatic Diseases (2014)

A recent pooled analysis of randomised trials found an increased risk of myocardial infarction with use of the antiosteoporotic drug strontium ranelate. We conducted a nationwide cohort study in Denmark, 2005-2011, to investigate the risk of acute coronary syndrome among postmenopausal women treated with strontium ranelate.The study involved two analytic setups. The first analysis included new users of either strontium ranelate (n=1798) or one of the two first-line bisphosphonates in Denmark (alendronate and risedronate; n=65 236). The second analysis included patients who had first been treated with a first-line bisphosphonate and subsequently switched to either strontium ranelate (n=1219) or ibandronate (n=2290). The primary outcome was acute coronary syndrome (unstable angina or myocardial infarction). The secondary outcome was any-cause mortality. Cox regression was used to estimate HRs, with adjustment using a disease risk score.Compared with use of alendronate/risedronate, use of strontium was not associated with significantly increased risk of acute coronary syndrome (rate per 1000 person-years 5.7 for strontium vs 6.3 for alendronate/risedronate; adjusted HR 0.89, 95% CI 0.52 to 1.55) or any-cause mortality (adjusted HR 0.96, 95% CI 0.76 to 1.21). In the analysis of switchers, strontium was not associated with significantly increased risk of acute coronary syndrome (rate per 1000 person-years 9.9 for strontium vs 9.9 for ibandronate; adjusted HR 1.00, 95% CI 0.49 to 2.05) or of any-cause mortality (adjusted HR 1.45, 95% CI 0.95 to 2.21).These real-world data of antiosteoporotic drug users do not support a significant association between use of strontium ranelate and acute coronary syndrome.
Method to detect substitutions in the interferon-sensitivity—Determining region of hepatitis C virus 1b for prediction of response to interferon therapy
Authors: Shuhei Nishiguchi, Tadashi Ueda, Teiji Itoh, Masaru Enomoto, Motoharu Tanaka, Nobuyuki Tatsumi, Katsuhiko Fukuda, Akihiro Tamori, Daiki Habu, Tadashi Takeda, Shuzo Otani, Susumu Shiomi
Journal: Hepatology (2001)

Substitutions deduced by direct sequencing in the interferon-sensitivity-determining region (ISDR) of hepatitis C virus (HCV) are related to patients' responses to interferon (IFN), but sequencing is time consuming and results are only for the dominant virus. We developed a rapid method to detect such changes. With serum from 50 patients with chronic hepatitis C (genotype 1b) given IFN-alpha, a way to detect changes in ISDR by hybridization with oligonucleotide probes that had a prototype nucleotide sequence of HCV-J was established. Hybridization intensity was expressed as optical density (OD(NS5A)). The method was checked with serum from 100 more patients. In the study of 50 patients, all 21 with the prototype sequences had a high OD(NS5A) (> or = 0.4), and all 8 patients with a mutant-type sequence had low values (< or = 0.2). Twelve (95% confidence interval, 36-81%) of 20 patients with OD(NS5A) of <0.4 and 2 (1%-22%) of 30 patients with OD(NS5A) > or = 0.4 had complete responses (CR). All nine (66%-100%) patients with OD(NS5A) <0.4 and little HCV RNA (<100 kIU/mL) had CR, but none (0%-14%) of the 24 patients with high values from both predictors had CR. In the study of 100 patients, OD(NS5A) and the HCV RNA level were independent predictors of the effects of IFN. By multivariate analysis, the odds ratio for a CR in patients with OD(NS5A) of > or = 0.4 was 0.015 (0. 001-0.190) compared with the other patients (P =.001). In conclusion, our method should be useful in identification of prototype strains, which generally resist IFN therapy.
Hypothyroidism presenting with musculoskeletal symptoms.
Authors: D N Golding
Journal: Annals of the Rheumatic Diseases (1970)

The possibility of hypothyroidism should be con- sidered in patients presenting with rheumatic pains of uncertain aetiology.While it is established that this condition can occasionally present with muscle weakness due to myopathy (Fessel, 1968), it is per- haps less well appreciated that muscle pain and stiff- ness may predominate over weakness, and in this paper nine hypothyroid patients who presented with musculoskeletal symptoms of this kind are described.Their principal features are summarized in Table I.This paper was presented at a meeting of The Heberden Society at Burgenstock, Switzerland, in June, 1968.Table I Clinical features in nine hypothyroid patients presenting with musculoskeletal symptoms Case no.
Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D.
Authors: S Balsan, M Garabédian, M Larchet, A M Gorski, G Cournot, C Tau, A Bourdeau, C Silve, C Ricour
Journal: Journal of Clinical Investigation (1986)

We report the beneficial effects of calcium infusions in a child with hereditary resistance to 1,25(OH)2D and alopecia. This patient after transient responsiveness to vitamin D derivatives became unresponsive to all therapy despite serum 1,25(OH)2D concentrations maintained at levels approximately 100-fold normal. A 7-mo trial with calcium infusions led to correction of biochemical abnormalities and healing of rickets. Bone biopsies (n = 3) showed a normal mineralization and the disappearance of the osteomalacia. Cultures of bone-derived cells demonstrated a lack of activation of 25-hydroxyvitamin D 24-hydroxylase and osteocalcin synthesis by 1,25(OH)2D3 (10(-9) and 10(-6) M). These results demonstrate that even in the absence of a normal 1,25(OH)2D3 receptor-effector system in bone cells, normal mineralization can be achieved in humans if adequate serum calcium and phosphorus concentrations are maintained; and calcium infusions may be an efficient alternative for the management of patients with this condition who are unresponsive to large doses of vitamin D derivatives.
Pharmacogenetics for Genes Associated with Age-related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT)
Authors: Stephanie A. Hagstrom, Gui-shuang Ying, Gayle J.T. Pauer, Gwen M. Sturgill-Short, Jiayan Huang, David G. Callanan, Ivana K. Kim, Michael L. Klein, Maureen G. Maguire, Daniel F. Martin
Journal: Ophthalmology (2013)
Cirripede Phylogeny Using a Novel Approach: Molecular Morphometrics
Authors: Bernard Billoud, Marie-Anne Guerrucci, Monique Masselot, Jean S. Deutsch
Journal: Molecular Biology and Evolution (2000)

We present a new method using nucleic acid secondary structure to assess phylogenetic relationships among species. In this method, which we term "molecular morphometrics," the measurable structural parameters of the molecules (geometrical features, bond energies, base composition, etc.) are used as specific characters to construct a phylogenetic tree. This method relies both on traditional morphological comparison and on molecular sequence comparison. Applied to the phylogenetic analysis of Cirripedia, molecular morphometrics supports the most recent morphological analyses arguing for the monophyly of Cirripedia sensu stricto (Thoracica + Rhizocephala + Acrothoracica). As a proof, a classical multiple alignment was also performed, either using or not using the structural information to realign the sequence segments considered in the molecular morphometrics analysis. These methods yielded the same tree topology as the direct use of structural characters as a phylogenetic signal. By taking into account the secondary structure of nucleic acids, the new method allows investigators to use the regions in which multiple alignments are barely reliable because of a large number of insertions and deletions. It thus appears to be complementary to classical primary sequence analysis in phylogenetic studies.
Respiratory disorders and atopy in Danish refuse workers.
Authors: T Sigsgaard, P Malmros, L Nersting, C Petersen
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

This survey describes respiratory and mucosal symptoms of garbage-handling and recycling workers in Denmark. The study includes 20 paper-sorting workers, eight compost workers, and 44 garbage-handling workers. As a control group, 119 workers from water purification plants of Copenhagen were chosen; workers in our study had a lower mean age and shorter mean employment time than did members of the control group. There was no significant difference in tobacco consumption between the groups. Garbage-handling workers were exposed to a significantly higher mean concentration (SD) of total dust than were water supply workers-0.74 (0.77) mg/m3 compared with 0.42 (0.25) mg/m3 (p < 0.05). Total count of microorganisms was significantly higher in garbage-handling and composting areas compared with paper-sorting as well as water supply areas 0.46 (0.125) x 10(5), 0.54 (0.77) x 10(5), 4.7 (5.89) x 10(3), and 0.08 (0.04) x 10(3) cfu/m3, respectively (p < 0.05). This difference could not be explained as an effect of differential growth requirements. Significantly higher amounts of gram-negative bacteria were found in composting and garbage-handling plants than in water-supply plants. In garbage-handling plants only, there were significantly higher amounts of endotoxins than in paper-sorting plants. Significantly higher prevalence of chest tightness (14%), flu-like symptoms (14%), itching eyes (27%), itching nose (14), and sore or itching throat (21%) were found among garbage-handling workers, compared with, respectively, 1, 1, 11 and 0% among water-supply workers. Furthermore, prevalence of nausea and vomiting or diarrhea rose from 2% and 7% among the water-supply workers to 19% and 27% among the garbage workers.(ABSTRACT TRUNCATED AT 250 WORDS)
Vitamin D status and longitudinal lung function decline in the Lung Health Study
Authors: K. M. Kunisaki, D. E. Niewoehner, R. J. Singh, J. E. Connett
Journal: European Respiratory Journal (2010)

Low blood vitamin D levels have been postulated to be a risk factor for worse lung function, based largely on cross-sectional data. We sought to use longitudinal data to test the hypothesis that baseline plasma 25-hydroxyvitamin D (25(OH)D) is lower in subjects with more rapid lung function decline, compared to those with slow lung function decline. We conducted a nested, matched case-control study in the Lung Health Study 3 cohort. Cases and controls were continuous smokers with rapid and slow lung function decline, respectively, over ~6 yrs of follow-up. We compared baseline 25(OH)D levels between cases and controls, matching date of phlebotomy and clinical centre. Among 196 subjects, despite rapid and slow decliners experiencing strikingly and significantly different rates of decline of forced expiratory volume in 1 s (-152 versus -0.3 mL·yr⁻¹; p < 0.001), there was no significant difference in baseline 25(OH)D levels (25.0 versus 25.9 ng·mL⁻¹; p = 0.54). There was a high prevalence of vitamin D insufficiency (35%) and deficiency (31%); only 4% had a normal 25(OH)D level in the winter. Although vitamin D insufficiency and deficiency are common among continuous smokers with established mild-to-moderate chronic obstructive pulmonary disease, baseline 25(OH)D levels are not predictive of subsequent lung function decline.
P270 Reducing Asthma Admissions by Improving Asthma Management
Authors: J Gibbs, A Hardwell, A Eagling
Journal: Thorax (2012)

<h3>Introduction</h3> There were 79,794 emergency hospital admissions for asthma in the UK in 2008–09 - an estimated 75% were avoidable [1]. Asthma admissions from Bristol GP practises contributed to this; over 600 people were admitted to hospital in this year because of their asthma. NHS Bristol set out to improve asthma management and reduce asthma hospital admissions across the Primary Care Trust <h3>Method</h3> Previous audits identified variations in asthma management across Bristol GP practises. Initial data searches identified some practises provided annual asthma reviews to 73.3% of their asthma register, others only 36.4%. Inhaler technique was checked in 60.8% of patients in some practises, in others only 16.9%. NHS Bristol commissioned NSHI Ltd* to run the IMPACT* service across Bristol GP practises to reduce these variations. The IMPACT service provided a therapeutic review, modular education and detailed clinical review by diploma trained asthma nurses, according to agreed practise protocols. Asthmatic patients were invited to attend a structured clinical review of their asthma. Patients were given a self-management plan and educated in better managing their condition. Practise staff were also provided with enhanced respiratory training. <h3>Results</h3> There has been a 19.5% reduction in asthma admissions in the period from February 2011–January 2012 in Bristol (n=37) compared to the previous year. There were 90 admissions in IMPACT practises (n = 13) and 303 admissions in non-IMPACT practises (n=43) during this period. The IMPACT practises have observed a reduction of 35.6%, and the non-IMPACT practises have observed a reduction of 12.4%. Overall, 13 IMPACT practises accounted for 54.7% of the reduction. <h3>Conclusion</h3> A structured approach to asthma management (including the provision of education to health care professionals in line with national asthma guidelines) and increasing patient awareness of asthma (including knowledge of how to manage their symptoms) can reduce variations in asthma care and hospital admissions. <h3>Reference</h3> Asthma UK for Journalists: Key facts and stats: www.asthma. uk.org (Viewed July 2012). *NSHI Ltd (National Services for Health Improvement). *Improving the Management of Patients Asthma and COPD Treatment. (IMPACT) is an independent nurse service sponsored by TEVA UK Limited.
Inhibition of Intracellular Transport of B Cell Antigen Receptor Complexes by Kaposi's Sarcoma–Associated Herpesvirus K1
Authors: Bok-Soo Lee, Xavier Alvarez, Satoshi Ishido, Andrew A. Lackner, Jae U. Jung
Journal: The Journal of Experimental Medicine (2000)

The B cell antigen receptor (BCR) is a large complex that consists of a disulfide-linked tetramer of two transmembrane heavy (mu) chains and two light (lambda or kappa) chains in association with a heterodimer of Igalpha and Igbeta. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a transforming protein called K1, which has structural and functional similarity to Igalpha and Igbeta. We demonstrate that K1 downregulates the expression of BCR complexes on the surface. The NH(2)-terminal region of K1 specifically interacts with the mu chains of BCR complexes, and this interaction retains BCR complexes in the endoplasmic reticulum, preventing their intracellular transport to the cell surface. Thus, KSHV K1 resembles Igalpha and Igbeta in its ability to induce signaling and to interact with mu chains of the BCR. However, unlike Igalpha and Igbeta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu chains to block the intracellular transport of BCR complexes to the cell surface. These results demonstrate a unique feature of the K1 transforming protein, which may confer virus-infected cells with a long-term survival advantage.
Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention in Multivessel Disease—Reply
Authors: Ilke Sipahi
Journal: JAMA Internal Medicine (2014)

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Utility of Routine Psychological Screening in the Childhood Cancer Survivor Clinic
Authors: Christopher Recklitis, Tara O’Leary, Lisa Diller
Journal: Journal of Clinical Oncology (2003)

This study examined the utility of routine psychologic screening in a childhood cancer survivor clinic by evaluating patient acceptance, comparing subjects' symptoms to normative data, examining the utility of specific tests, and identifying risk factors associated with psychological distress.During their annual clinic visit, 101 adult survivors of childhood cancer (median age, 25 years) completed the Symptom Checklist 90 Revised (SCL-90), as well as the Short Form 36 (SF-36), Beck Depression Inventory (BDI), and one additional suicide question. Psychological distress was operationally defined according to the published SCL-90 clinical case rule, classifying subjects with a consistent pattern of symptom elevations as clinical cases.The majority of subjects (80%) completed the screening in less than 30 minutes and reported little (15%) or no (84%) distress. Sixty-four percent believed it would help "very much" or "moderately" in getting to know them, and 35% thought it would help "slightly." On the SCL-90, 32 subjects (31.7%) had a positive screen, indicating significant psychological distress. All subjects with clinically significant symptoms on the BDI and SF-36 Mental Health Scale were cases on the SCL-90 (case-positive). Suicidal symptoms were reported in 13.9% of the sample, all of whom were SCL-90 cases. In a logistic regression model, subjects' dissatisfaction with physical appearance, poor physical health, and treatment with cranial radiation were associated with psychological distress.Results demonstrate that routine psychological screening can be successfully integrated into the cancer survivor clinic and may be effective in identifying those survivors with significant distress who require further evaluation.
Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation
Authors: A. Van Muylem, C. Melot, M. Antoine, C. Knoop, M. Estenne
Journal: Thorax (1997)

Lung function is altered by infection and rejection in patients who undergo heart-lung transplantation. The sensitivity, specificity, and positive/negative predictive values (PPV and NPV) of lung function for the detection of allograft dysfunction in these patients were measured.Thirty three patients who underwent heart-lung transplantation were followed for a mean period of 16.3 months. On 123 occasions functional measurements were obtained at the time a transbronchial biopsy specimen and/or bronchoalveolar lavage fluid was taken, which were used as gold standards. Optimal sensitivity (the value for which sensitivity equals specificity) was computed for each functional test from receiver-operator characteristic (ROC) curves.Acute rejection was present on 31 occasions and infection on 36 occasions; 56 samples were normal. Infection and rejection were accompanied by airflow obstruction, a rise in the slopes of the alveolar plateaus for nitrogen, hexafluoride sulphur and helium (SN2, SSF6, and SHe), and a decrease in the difference between SSF6 and SHe (delta S), total lung capacity (TLC), and lung transfer factor (TLCO). Optimal sensitivities for SHe, mid forced expiratory flow (FEF25-75), TLC, and forced expiratory volume in one second (FEV1) were 68%, 67%, 66%, and 60%, respectively; they were not different for infection and rejection and did not change over the study period. For infection and rejection together, PPV ranged from 72% to 88% and NPV from 27% to 52% according to the functional test and the postoperative period considered.Indices of ventilation distribution, FEF25-75, and TLC have the best optimal sensitivity for the diagnosis of infection and rejection after heart-lung transplantation. The high PPV of pulmonary function in detecting allograft dysfunction observed in this study suggests that a diagnostic procedure should be performed whenever one or more functional tests deteriorate; conversely, the low NPV indicates that a stable pulmonary function does not rule out allograft dysfunction.
Statistical Methods for Risk-Outcome Research: Being Sensitive to Longitudinal Structure
Authors: David A. Cole, Scott E. Maxwell
Journal: Annual Review of Clinical Psychology (2009)

The relation between risk and outcome consists of myriad, complex, longitudinal processes. To study these relations requires research designs and statistical methods that are sensitive to the longitudinal structure of the risk, the outcome, and the risk-outcome relation. This review presents four longitudinal characteristics that can complicate psychopathology risk-outcome research. We represent each complication with an example data set. We demonstrate how conventional statistical approaches can yield highly misleading results. Finally, we review alternative statistical approaches that can handle these complications quite well.
Emergence and Evolutionary Analysis of the Human DDR Network: Implications in Comparative Genomics and Downstream Analyses
Authors: Aida Arcas, Oscar Fernández-Capetillo, Ildefonso Cases, Ana M. Rojas
Journal: Molecular Biology and Evolution (2014)

The DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. This network is an ensemble of distinct but often overlapping subnetworks, where different components fulfill distinct functions in precise spatial and temporal scenarios. To understand how these elements have been assembled together in humans, we performed comparative genomic analyses in 47 selected species to trace back their emergence using systematic phylogenetic analyses and estimated gene ages. The emergence of the contribution of posttranslational modifications to the complex regulation of DDR was also investigated. This is the first time a systematic analysis has focused on the evolution of DDR subnetworks as a whole. Our results indicate that a DDR core, mostly constructed around metabolic activities, appeared soon after the emergence of eukaryotes, and that additional regulatory capacities appeared later through complex evolutionary process. Potential key posttranslational modifications were also in place then, with interacting pairs preferentially appearing at the same evolutionary time, although modifications often led to the subsequent acquisition of new targets afterwards. We also found extensive gene loss in essential modules of the regulatory network in fungi, plants, and arthropods, important for their validation as model organisms for DDR studies.