tbuckley/cabot-search huggingface dataset:
Single-nucleotide polymorphism in the SCCmec-orfX junction distinguishes between livestock-associated MRSA CC398 and human epidemic MRSA strains
Authors: U Reischl, J Frick, S Hoermansdorfer, H Melzl, M Bollwein, H J Linde, K Becker, R Köck, C Tuschak, U Busch, A Sing
Journal: Eurosurveillance (2009)

A number of real-time PCR assays for direct detection of methicillinresistant (MRSA) in clinical specimens are targeting staphylococcal cassette chromosome mec (SCCmec) right extremity sequences and the S. aureus chromosomal orfX gene sequences located to the right of the SCCmec integration site. When testing 184 MRSA strains of human and animal origin from geographically distinct locations, we identified several characteristic single-nucleotide polymorphisms (SNPs) within the SCCmec-orfX junction of livestock-associated (LA) MRSA CC398 which serve as suitable strain markers for screening purposes. Within an assay time of 60 minutes and an additional 10 minutes for the melting curve analysis, all MRSA CC398 isolates were correctly identified by their characteristic T(m) value in the commercial LightCycler MRSA Advanced test. Studies to confirm the diagnostic accuracy of the SNP-based strain identification assay with a larger collection of clinical and LA-MRSA strains are ongoing.
Abstract 3421: Sox2 Converts Human Mesoangioblasts into Nanog-Expressing Multipotent Cells with Enhanced Cardiac Repair
Authors: Masamichi Koyanagi, Chang-Hwan Yoon, Masayoshi Iwasaki, Jes-Niels Boeckel, Janina Trauth, Stefan Rupp, Dietmar Schranz, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2008)

Induced pluripotent cells (iPS) were generated by overexpression of four factors (Oct3/4, Klf4, c-myc and Sox2) in fibroblasts and showed similar characteristic as embryonic stem (ES) cells. In contrast to iPS and ES cells, adult stem cells have a reduced plasticity. Therefore, we investigated whether reconstitution of the four pluripotency genes in adult progenitor cells improves their therapeutic capacity. Circulating mesoangioblasts (cMAB) have been recently identified in peripheral blood and showed distinct marker expression to bone marrow-derived stem cells and endothelial progenitor cells. cMAB are clonally expandable and exhibit high telomerase activity. cMAB expressed the pluripotency genes Oct3/4, KLF4, and c-Myc, whereas Sox2 and another important stemness gene, Nanog was not expressed. Since only Sox2 was absent out of the four pluripotency genes, we hypothesized that Sox2 transduction may be sufficient to induce pluripotency. Sox2 was overexpressed by lentiviral vector. Interestingly, Sox2-tranduced cMAB not only express Sox2 but also re-express the stem cell gene Nanog. Controls confirmed that the constitutively expressed genes, Oct3/4, KLF4, and c-myc, remained present after Sox2 transduction. Sox2-transduced cMAB formed embryoid body-like structures in culture. In order to test whether Sox2-transduced cells may exhibit improved therapeutic potential, we injected Sox2-transduced cMABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-overexpressing cells, cardiac function was improved compared to mice treated with control cells (LVEDV/weight; 1.34 ± 0.14 vs 1.88 ± 0.02 μl/g, LVEDP; 13.2 ± 1.0 vs 18.7 ± 2.6 mmHg, dp/dt max; 7989 ± 1030 vs 6331 ± 149 mmHg/s, dp/dt min; 6583 ± 683 vs 4792 ± 514 mmHg/s, and Tau; 9.2 ± 0.8 vs 11.6 ± 1.8 ms, respectively). In summary, the complementation of Sox2 in Oct3/4-, Klf4-, and c-myc-expressing cMABs induced Nanog expression and improved the cardiac regeneration capacity of these circulating adult stem cells.
Cigarette smoke extract and TGF-β1 induce distinctive expression of extracellular matrix protein genes in human airway smooth muscle cells
Authors: Ling Chen, Qi Ge, Juith Black, Janette Burgess, Brian Oliver
Journal: European Respiratory Journal (2013)

Introduction: The increased thickness of airway wall in COPD is related to the abnormal deposition of extracellular matrix (ECM) proteins. Cigarette smoking and TGF-β1 are likely involved in the pathological progress. This study aimed to compare the ECM protein gene expression in COPD and non COPD airway smooth muscle (ASM) cells stimulated by cigarette smoke extract (CSE) or TGF-β1.  Methods: Human ASM cells obtained from smoking donors with (n=3) or without COPD (n=3) were stimulated with 5% CSE or 10ng/ml TGF-β1. RNA lysates were collected and pooled then 84 ECM and adhesion molecule related genes were examined by real time PCR. Data were normalized to 18S rRNA and expressed as fold change compared with control. A cut off of 2 fold was used to indicate up-regulation.  Results: In ASM cells 70 genes can be detected at basal condition. TGF-β1 up-regulated 27 of these genes in COPD ASM cells, and 28 genes in non-COPD ASM cells. CSE up-regulated 44 and 36 of the 70 genes in COPD and non COPD ASM cells, respectively. Among the genes up-regulated by CSE, 5 genes (collagen type I, V, VIII, XV, and thrombospondin 2) were expressed more than 1.5 times higher in COPD than non COPD ASM cells. In contrast, 6 genes (matrix metalloproteinases 1, 12, 14, ADAM metalloproteinases with thrombospondin type 1, 8, and selectin L) were at least 1.5 times lower in COPD than non COPD ASM cells.  Conclusions: Overall CSE up-regulated more ECM protein genes than TGF-β1. In particular, collagen genes were up-regulated to a greater extent in COPD versus non-COPD ASM cells. However, CSE induced matrix metalloproteinase genes had impaired up-regulation in COPD cells.
Angiographic Predictors of 6-Month Patency of Bypass Grafts Implanted to the Right Coronary Artery
Authors: David Glineur, William D’hoore, Gebrine El Khoury, Sixte Sondji, Gregory Kalscheuer, Jean-Christophe Funken, Jean Rubay, Alain Poncelet, Parla Astarci, Robert Verhelst, Philippe Noirhomme, Claude Hanet
Journal: Journal of the American College of Cardiology (2008)
Efficacy and safety of linezolid for the treatment of multidrug resistant tuberculosis (MDR-TB) and disease by non tuberculous mycobacteria (NTM)
Authors: Maria Ralli, Lambrini Stournara, Emily G. Tsaroucha, Maria Palavra, Spyridon Karagiannis, Vassilios Sgountzos, Apostolos Papavassiliou
Journal: European Respiratory Journal (2011)

Linezolid9s (L) long-term use in the treatment of MDR-TB and NTM may be limited by its serious adverse reactions. Aim of this study was to evaluate the efficacy and tolerability of a daily dose of 600 mgr of L in combination with other drugs against mycobacteria, in patients with culture proven MDR-TB and NTM disease.   Method:  Between Sept 2008 and Jan 2011 in our TB Unit/Outpatient Clinic we followed 34 MDR-TB + XDR-TB and 18 NTM pts. Of them, 19 pts (2 XDR, 4 NTM), all HIV (–), had been treated with L which was added to regimens for 4-24 months (median 17). Sputum cultures, blood count/chemistry, ophalmologic and neurologic examination were undertaken on a regular basis.   Results:  16 pts completed treatment and were cured. Cultures became negative in all pts in an average of 14–32 weeks. One died after 5 months of treatment due to chronic respiratory failure and progressive M. avium disease, 2 discontinued (no adherence) after 5 and 7 months. 3 of 16 pts experienced adverse events, which led to withdrawal of L in all 3. 2 pts developed bone marrow depression and one optic neuropathy. Blood transfusions were given to both pts and bone marrow function normalized after cessation of L.   Conclusion:  Linezolid seems highly effective in combination treatment of MDR-TB, XDR-TB and NTM disease. The majority of patients on L had positive treatment outcomes. All pts under L treatment should be monitored closely for presence of serious adverse reactions.
Indole-3-Carbinol Synergizes with and Restores Fludarabine Sensitivity in Chronic Lymphocytic Leukemia Cells Irrespective of p53 Activity and Treatment Resistances
Authors: Gema Perez-Chacon, Carolina Martinez-Laperche, Nerea Rebolleda, Beatriz Somovilla-Crespo, Cecilia Muñoz-Calleja, Ismael Buño, Juan M. Zapata
Journal: Clinical Cancer Research (2015)

Chronic lymphocytic leukemia (CLL) still is lacking a cure. Relapse and development of refractoriness to current treatments are common. New therapies are needed to improve patient prognosis and survival.Indole-3-carbinol (I3C) is a natural product with antitumor properties already clinically tested. The effect of I3C, F-ara-A, and combinations of both drugs on CLL cells from patients representing different Rai stages, IGHV mutation status, cytogenetic alterations, p53 functionality, and treatment resistances was tested, as well as the toxicity of these treatments in mice.I3C induces cytotoxicity in CLL cells but not in normal lymphocytes. I3C strongly synergized with F-ara-A in all CLL cells tested, including those with p53 deficiency and/or F-ara-A resistance. The mechanism of cell death involved p53-dependent and -independent apoptosis. The combination of I3C + F-ara-A was equally effective in CLL cells irrespective of IGHV mutation stage and patient refractoriness. Moreover, CLL survival and treatment resistance induced by co-culturing CLL cells on stroma cells were overcome by the combinatory I3C + F-ara-A treatment. No toxicity was associated with the combined I3C + fludarabine treatment in mice.I3C in combination with F-ara-A is highly cytotoxic in CLL cells from refractory patients and those with p53 deficiency. The striking dose reduction index for F-ara-A in combination with I3C would reduce fludarabine toxicity while having a similar or better anti-CLL effectiveness. Moreover, the low toxicity of I3C, already clinically tested, supports its use as adjuvant and combinatory therapy in CLL, particularly for patients with relapsed or refractory disease.
NCCN Increases the Emphasis on Genetic/Familial High-Risk Assessment in Colorectal Cancer
Authors: Heather Hampel
Journal: Journal of the National Comprehensive Cancer Network (2014)

NCCN has developed new guidelines for the assessment of high-risk familial/genetic colorectal cancer, and has positioned these recommendations within the guidelines for detection, prevention, and risk reduction. The Panel recommends that all patients with colorectal cancer be screened for Lynch syndrome, which occurs in 1 of every 35 patients and is the most common form of hereditary colorectal cancer. Such screening could be universal so that all tumors are genetically tested, or screening could be restricted to patients under the age of 70 and those aged 70 and older who meet clinical criteria.
Is It Ethical to Enroll Cognitively Impaired Adults in Research That Is More Than Minimal Risk With No Prospect of Benefit?
Authors: Holly A. Taylor, Ellen Kuwana, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2015)

"Is It Ethical to Enroll Cognitively Impaired Adults in Research That Is More Than Minimal Risk With No Prospect of Benefit?." The American Journal of Bioethics, 15(10), pp. 64–65
The progression of NAFLD to NASH in a mouse model of Hfe(-/-)- associated steatohepatitis is attenuated by co-administration of curcumin and vitamin E
Authors: Lesley Jaskowski, Ashley S. Wilkinson, Laurence Britton, Terrence C. Tan, Andrew D. Clouston, Kim Bridle, Gregory J. Anderson, Graeme A. Macdonald, Linda M. Fletcher, V. Nathan Subramaniam, Darrell H. Crawford
Journal: Hepatology (2012)
Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study Commentary: Management in paediatric and adult cystic fibrosis centres improves clinical outcome
Authors: R. Mahadeva, K. Webb, R. C Westerbeek, N. R Carroll, M. E Dodd, D. Bilton, D. A Lomas, J A Dodge
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To assess the effect on clinical outcome of managing paediatric and adult patients with cystic fibrosis at specialised cystic fibrosis centres. <b>Design:</b> Cross sectional study. <b>Setting:</b> Two adult cystic fibrosis centres in the United Kingdom. <b>Subjects:</b> Patients from an adult cystic fibrosis centre in Manchester were subdivided into those who had received continuous care from paediatric and adult cystic fibrosis centres (group A), and those who had received paediatric care in a centre not specialising in cystic fibrosis followed by adult care in a cystic fibrosis centre (group B). Group C were referrals to the new adult cystic fibrosis centre in Cambridge who had received neither paediatric nor adult centre care for their cystic fibrosis. <b>Main outcome measures:</b> Body mass index (weight (kg)/height (m<sup>2</sup>)), lung function (forced expiratory volume in one second (FEV<sub>1</sub> percentage of predicted)), the Northern chest <i>x</i> ray film score, and age at colonisation with <i>Pseudomonas aeruginosa</i>. <b>Results:</b> A prominent stepwise increase in body mass index was associated with increasing amounts of care at a cystic fibrosis centre; 18.3, 20.2, and 21.3 for groups C, B, and A respectively (P&lt;0.001). Improved nutritional status was correlated with a higher FEV<sub>1</sub> and better (lower) chest <i>x</i> ray film scores; r=0.52 and −0.45 respectively (P&lt;0.001 for both). <b>Conclusion:</b> These findings provide the first direct evidence that management of cystic fibrosis in paediatric and adult cystic fibrosis centres results in a better clinical outcome, and strongly supports the provision of these specialist services. <h3>Key messages</h3> Management of patients with cystic fibrosis in paediatric and adult cystic fibrosis centres results in an improved clinical outcome Improved clinical outcome occurred in cystic fibrosis centres despite earlier and more frequent colonisation with <i>Pseudomonas aeruginosa</i> Nutritional status is an important predictor of lung disease in cystic fibrosis
The economic impact of psychotherapy: a review
Authors: G O Gabbard, S G Lazar, J Hornberger, D Spiegel
Journal: American Journal of Psychiatry (1997)

Objective: The authors reviewed data involving the impact of providing psychotherapy for psychiatric disorders on costs of care.Method: In a search of the MEDLINE database limited to peer-reviewed papers published from 1984 through 1994, 686 articles were identified.Forty-one articles, covering 35 studies, were found in which the intervention tested was psychotherapeutic and the study included measures of outcome that had some implications for cost.The exclusion criteria for reviewing these studies included absence of a comparison group, a focus on medical disorders instead of psychiatric illnesses, and outcomes that did not include cost data or measures from which costs could be inferred.On this basis, 18 of the 35 studies were selected for analysis.The studies were categorized according to whether or not subjects were randomly assigned to study groups.Two reviewers independently read each study to identify the following characteristics: inclusion criteria, exclusion criteria, types of interventions, main outcome variables, sample size, and statistical tests for significant differences between treatments.Outcomes had to include actual cost accounting or data on medical care utilization or work functioning.Results: The findings of eight (80%) of the 10 clinical trials with random assignment and all eight (100%) of the studies without random assignment suggested that psychotherapy reduces total costs.Conclusions: Psychotherapy appears to have a beneficial impact on a variety of costs when used in the treatment of the most severe psychiatric disorders, including schizophrenia, bipolar affective disorder, and borderline personality disorder.Much of that impact accrues from reductions in inpatient treatment and decreases in work impairment.
Toxicity, Efficacy, and Pharmacology of Suramin in Adults With Recurrent High-Grade Gliomas
Authors: Stuart A. Grossman, Surasak Phuphanich, Glenn Lesser, Jack Rozental, Louise B. Grochow, Joy Fisher, Steven Piantadosi
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the toxicity, efficacy, and pharmacology of suramin in patients with recurrent or progressive recurrent high-grade gliomas. PATIENTS AND METHODS: Fifty adults were to receive suramin. However, if no responses were seen in the first ten patients, the study was to be terminated. A total of 12 patients were enrolled onto this trial. Ten patients had glioblastoma multiforme, and 11 had received prior nitrosoureas. RESULTS: Drug-related toxicities were modest and reversible. Three patients developed grade 3 to 4 neutropenia, constipation, diarrhea, or nausea. No CNS bleeding was observed. Median time to progression was 55 days (range, 17 to 242 days) and median survival was 191 days (range, 42 to 811 days). No partial or complete responses were seen at 12 weeks. However, the clinical outcome of three patients suggests that evidence of suramin activity may be delayed. One patient who “progressed” after 12 weeks of suramin had a subsequent marked reduction in tumor size and has maintained an excellent partial response for over 2 years without other therapy. Two others had disease stabilization and lived for 16 and 27 months. Pharmacokinetics from 11 patients revealed that all reached target suramin concentrations. CONCLUSION: This study demonstrates that suramin is well tolerated by patients with recurrent high-grade gliomas and may have efficacy in this disease. Its pharmacology seems unaffected by anticonvulsants. As a result of this data, suramin and radiation are now being administered concurrently to patients with newly diagnosed glioblastoma multiforme, with survival as the primary outcome.
An analysis of sentinel events after the implementation of a comprehensive information technology system for a new cancer center
Authors: P. J. Manno, N. Vogelzang, S. Sharma, A. Pomerantz, L. Fink, P. Halterman, S. Caramico, R. Faircloth, S. Murdock
Journal: Journal of Clinical Oncology (2007)

17047 Background: The Nevada Cancer Institute (NVCI) is the cancer center for the state of NV conducting basic and clinical research and services in medical oncology, hematology, radiation oncology, laboratory medicine, pathology, and imaging. With the national mandate for electronic medical records (EMR), we focused on selecting a comprehensive EMR/IT system during the planning of the NVCI.. The goal was to have a seamless interface between clinical services and financial management, to maintain an extensive database of pt outcomes linked to demographics for future data mining. We hypothesized that an EMR would lead to improved safety and efficiency in patient care. Methods: Pt visits began 3/05 with paper records while EMR systems were being reviewed. Ultimately, IMPAC Medical Systems, Inc was selected. After extensive testing and re-configuration of an existing IMPAC system by the IT department and extensive training sessions, a rapid transition from paper records to a complete paperless environment occurred 9/05. As of 12/31/06, we have seen 1,271 patients. Since the care plans, lab interface and drug bar coding were in place by 4/06, we reviewed the interval of 4–12/06 for efficacy of charge capture, reduction in medication errors, the tracking of patients in ancillary services, the development of a 3 tier approval system for drug orders, and the voice recognition system for its efficiency in reducing transcription costs and turnaround time. Results: In that interval, we recorded 3617 patient visits in the medical oncology infusion center and 4766 in radiation oncology. There were 0 sentinel events. Only 2 medication errors were made which were attributed to human error but not related to the software itself. Conclusions: These safety data appear superior to comparable error rates in a paper environment.We appear to have enhanced pt safety, reduced the costs of lost revenue, increased access to the patient record and created an opportunity to analyze pt data on a longitudinal basis. We are increasing our future reporting by implementing the IMPAC Quantros Safety and Risk Management System. No significant financial relationships to disclose.
Relationship between psychological well-being and lung health status in patients with bronchectasis
Authors: Leila Boussoffara, Nadia Boudawara, Ines Hammami, Ahmed Ben Saad, Mounira Sakka, Jalel Knani
Journal: European Respiratory Journal (2011)

Introduction:  Patients with bronchectasis often experience depression and anxiety, but little information is available regarding patients with these conditions.   Aim of the study:  This study was carried out to examine levels of anxiety and depression in patients with bronchectasis.   Methods:  Fourty three patients with bronchectasis, determined by high resolution computed tomography scan, completed anxiety and depression questionnaires.   Results:  27% of patients had minor depression with an anxiety depression score more than 13 and 9% of patients had severe depression with an anxiety depression score more than 19. The anxiety depression status was not correlated to the extent of bronchectasis on CT scan (p=0,362). Post-bronchodilator FEV1 and higher airflow limitation were associated to a severe anxiety depression status.   Conclusion:  Anxiety and depression are quite common in bronchectasis. Treatment in bronchectasis aimed essentially at reducing symptoms but it will not reduce levels of anxiety and depression witch need alternative therapy.
Monitoring safety of over the counter drugs
Authors: A. G Wade
Journal: BMJ (2002)

Editor—Clark et al raise an important issue related to the safety of drugs, both over the counter drugs and those provided by a pharmacy.1 As increasing numbers of drugs are licensed to be sold over the counter, there is a growing need for both the safety of the drugs and their interactions with prescribed drugs to be carefully monitored.

The solution proposed for pharmacy medicines seems to me to be dogged by the problems faced by current systems of surveillance of prescribed drugs—that is, under-reporting engendered by complicated systems, the time lag, and expense. Over the counter medicines present an even greater problem.

The philosophy of switching to pharmacy medicines or over the counter medicines is to empower the patient to participate more fully in his or her health care. Why not extend the same philosophy to safety monitoring? A card enclosed with the drug would invite all users to register as consumers—we already do this for consumer electrical products. Simple postal questionnaires supplemented if necessary by telephone follow up can provide good quality data not only on side effects but also on efficacy.2 My unit has conducted two successful pilot studies based on this model and is currently attempting to set up a full scale trial.