tbuckley/cabot-search huggingface dataset:
Glucocorticoid‐Induced Leucine Zipper Governs the Therapeutic Potential of Mesenchymal Stem Cells by Inducing a Switch From Pathogenic to Regulatory Th17 Cells in a Mouse Model of Collagen‐Induced Arthritis
Authors: P. Luz‐Crawford, G. Tejedor, A. L. Mausset‐Bonnefont, E. Beaulieu, E. F. Morand, C. Jorgensen, D. Noël, F. Djouad
Journal: Arthritis & Rheumatology (2015)

Objective Mesenchymal stem cells (MSCs) are potent immunosuppressive cells that have shown promise in the treatment of rheumatoid arthritis (RA). Deciphering the intrinsic characteristics of MSCs that correlate with their biologic activity will facilitate their clinical use. Recently, the role of glucocorticoid‐induced leucine zipper (GILZ) in the development of RA has been documented. The aim of this study was to evaluate whether GILZ expression by MSCs may contribute to their therapeutic effect. Methods MSCs were isolated from GILZ‐deficient (GILZ −/− ) mice and wild‐type mice. MSCs (1 × 10 6 cells) were injected twice via the tail vein into mice with collagen‐induced arthritis (CIA). Results In vitro, we showed that GILZ is a key factor involved in the immunosuppressive potential of MSCs. MSCs derived from GILZ −/− mice did not suppress the proliferation of CD4+ T cells and were less efficient than MSCs derived from WT mice in altering Th17 cell polarization. Thus, we investigated the role of GILZ in an experimental model of arthritis and demonstrated that although WT MSCs significantly reduced paw swelling in arthritic mice, GILZ −/− MSCs did not. Moreover, the magnitude of the effects of GILZ −/− MSCs on Th17 cell frequency was significantly lower than that of WT MSCs. The therapeutic effect of MSCs correlated with the generation of Treg cells bearing the CD4 + RORγt+IL‐17 low IL‐10+ signature, and Th17 cell polarization was GILZ dependent. Conclusion This study demonstrates that GILZ has an essential role in the therapeutic effectiveness of MSCs in arthritis by favoring Th17 cell polarization toward a regulatory phenotype. Therefore, potentiation of GILZ expression in MSCs could represent a means to enhance their therapeutic effect in autoimmune diseases.
Gujurat scheme to pay people to use toilets gets mixed response
Authors: S. Bagcchi
Journal: BMJ (2015)

A municipal corporation in Gujarat has said that it will pay people Rs1 (£0.01; €0.01; $0.02) when they use public toilets in a bid to stop open defecation.

Paresh Chaudhary, from the Ahmedabad Municipal Corporation, told the Press Trust of India that its “use and get paid” scheme would be up and running by 19 June.1 

“We have around 315 public toilets in the city,” Pravin Patel, chairman of the standing committee told the news agency. …
Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall Survival
Authors: Chul Kim, Vinay Prasad
Journal: JAMA Internal Medicine (2015)

ings could be due to a chance or unmeasured confounding and need confirmation in other studies, they do represent the first analytical data of this potential association.If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease 6 or to the emergence of a de novo demyelinating disease. 1 The rarity of demyelinating diseases limited the statistical power and capacity to adjust for or match on potential confounder variables.Thus, the estimates should be interpreted with caution because confounding cannot be excluded.
The "lonely predicament"
Authors: G. Colville
Journal: BMJ (2015)

As a child psychologist I am sometimes asked to see children in families where a death is anticipated. The assumption is that I will help them understand more about the illness and provide a safe space in which they can express their feelings about what is happening. But surprisingly often my young patients have made it quite clear that this is not something they want to do.

Occasionally they go on to talk more openly, but more commonly they …
Early detection of cardiotoxicity during chemotherapy using biomarkers
Authors: D. J. Lenihan, M. R. Massey, K. Baysinger, D. Steinert, L. Fayad, S. W. Yusuf, A. Chiu, J. Durand, E. T. Yeh
Journal: Journal of Clinical Oncology (2007)

19521 Cancer chemotherapy (CHEMO), especially anthracycline-containing regimens, may result in heart failure and left ventricular dysfunction (LVD) due to cardiotoxicity (CVTx). The ability to detect CVTx currently utilizes techniques to assess LVD, such as MUGA or echocardiography (Echo), which have substantial limitations and only detect LVD well after it occurs. Cardiac biomarkers, troponin (Trop I) and B-Type Natriuretic Peptide (BNP) are well established for detecting myocardial injury and LVD in patients without cancer. Limited evidence suggests that these may be important predictors of subsequent CVTx during CHEMO, but these markers have not been systematically investigated prospectively. Methods: Patients undergoing anthracycline-containing combination CHEMO were evaluated at baseline with: history and physical; electrocardiogram; Echo; and BNP and Trop I. Biomarkers were repeated before and after up to 6 cycles of CHEMO. ECHO was repeated after 6 cycles or at 6 months from baseline. Cardiac events (heart failure, LVD, sudden death, or arrhythmia) were documented, if present. Results: To date, 111 (53M/58F) patients, age 56±14 (mean±SD), with either lymphoma (n=39, 35%), sarcoma (n=60, 54%), or breast cancer (n=12, 11%) were enrolled. At least one traditional cardiac risk factor was identified in 77 (69%) and 2 or more risk factors noted in 46 (41%). Baseline ECHO parameters including ejection fraction (EF) and biomarkers were normal. With CHEMO, the mean post CHEMO BNP value (pg/ml) for the group did not change significantly; however, in the 8 patients with cardiac events, the BNP post CHEMO was elevated. The Trop I values were not abnormal except in 2 patients with events. Conclusion: Preliminary data collected to date indicates that BNP values during CHEMO remain normal unless cardiac events occur. Additionally, elevated BNP levels appear to detect CVTx, but LVEF did not. Furthermore, patients receiving CHEMO frequently have cardiac risk factors that may promote CVTx. [Table: see text] No significant financial relationships to disclose.
A quantitative method for the detection of spliced X-box binding protein-1 (XBP1) mRNA in primary bronchial epithelial cells (PBEC) as a measure of endoplasmatic reticulum (ER) stress
Authors: Annemarie van Schadewijk, Emily F.A. van 't Wout, Jan Stolk, Pieter S. Hiemstra
Journal: European Respiratory Journal (2011)

Accumulation of unfolded or misfolded proteins in the ER can cause ER stress, which is increasingly seen in diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency and Alzheimer disease. ER stress leads to the activation of the unfolded protein response (UPR). UPR signaling involves splicing of XBP1 mRNA and leads to the induction of the chaperone protein BiP and the transcription factor CHOP, which is a key-signaling component of ER-stress induced apoptosis. In present studies, XBP1 splicing is frequently used as an important marker for ER-stress and is visualized by gel electrophoresis which is laborious and difficult to quantify. The aim of this study was to develop and validate a quantitative RT-PCR (qPCR) which detects only the spliced form of XBP1 mRNA. We stimulated PBEC with thapsigargin and tunicamycin, both known ER-stress inducers, and performed a qPCR with primers that were designed to recognize only the spliced form of XBP1. We also performed qPCR for CHOP and BiP and correlated this with the spliced XBP1 mRNA to validate the results. The spliced XBP1 PCR product was also confirmed by DNA sequencing. The correlation of XBP1 splicing with the induction of CHOP and BiP was r=0.962 (p  This study was supported in part by a grant from the Netherlands Asthma Foundation.
The Effect of Local Roentgen Irradiation on the Biological Behavior of a Transplantable Mouse Carcinoma. I. Increased Frequency of Pulmonary Metastasis&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Henry S. Kaplan, Edwin D. Murphy
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article The Effect of Local Roentgen Irradiation on the Biological Behavior of a Transplantable Mouse Carcinoma. I. Increased Frequency of Pulmonary Metastasis Get access Henry S. Kaplan, M. D., Henry S. Kaplan, M. D. radiologist Search for other works by this author on: Oxford Academic PubMed Google Scholar Edwin D. Murphy, M. D. Edwin D. Murphy, M. D. pathologist National Cancer Institute, National Institutes of Health, Public Health Service, Federal Security Agency Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 9, Issue 5-6, April-June, Pages 407–413, https://doi.org/10.1093/jnci/9.5-6.407 Published: 01 April 1949 Article history Received: 08 October 1948 Published: 01 April 1949
Antibody‐Secreting Cell Specificity in Labial Salivary Glands Reflects the Clinical Presentation and Serology in Patients With Sjögren's Syndrome
Authors: Jacen S. Maier‐Moore, Kristi A. Koelsch, Kenneth Smith, Christopher J. Lessard, Lida Radfar, David Lewis, Biji T. Kurien, Nina Wolska, Umesh Deshmukh, Astrid Rasmussen, Kathy L. Sivils, Judith A. James, A. Darise Farris, R. Hal Scofield
Journal: Arthritis & Rheumatology (2014)

The serologic hallmark of primary Sjögren's syndrome (SS) is the presence of IgG antibodies specific for Ro (SSA) and La (SSB). The molecular characteristics of gland-derived B cells at the site of primary SS inflammation have been described previously; however, parallels between glandular antibody-secreting cells (ASCs) and serologic antibody specificities have not been evaluated. We used recombinant monoclonal antibody (mAb) technology to study the specificities of salivary gland (SG)-derived ASCs, evaluate their molecular characteristics, and identify IgG antibody specificity.Human antibodies were generated from glandular IgG ASCs. Heavy chain and light chain use and immunoglobulin subclass were analyzed by sequencing. Enzyme-linked immunosorbent assay, indirect immunofluorescence, enzyme immunoassay, and (35) S-labeled protein immunoprecipitation analysis were used to determine antibody specificity.Evaluation of single ASCs in SG biopsy specimens from a patient with primary SS and a patient with SS and overlapping systemic lupus erythematosus revealed significant concordance between serum autoantibody and glandular ASC specificities. Gland-derived ASC heavy chains and light chains were extensively somatically hypermutated, which is indicative of antigen-driven responses. Specifically, we produced the first fully human mAb derived from SGs.In patients with SS, the SGs are a site for the production of antibodies that extend beyond the canonical Ro and/or La SS specificities. Glandular antibody production strongly reflected the serologic humoral response in the 2 patients whom we studied.
Learning Clinical Reasoning.
Authors: P. Kassirer Jerome, B. Wong John, I. Kopelman Richard
Journal: Annals of Internal Medicine (1991)

Part I: THE PROCESSES OF CLINICAL REASONING 1: Overview 2: Diagnostic Hypothesis Generation 3: Refinement of Diagnostic Hypotheses 4: Use and Interpretation of Diagnostic Tests 5: Causal Reasoning 6: Diagnostic Verification 7: Therapeutic Decision Making 8: Examining Evidence 9: Cognitive Errors 10: Some Cognitive Concepts 11: Learning Clinical Problem Solving Part II: COGNITION AT THE BEDSIDE: A SET OF EXAMPLES 12: Introduction to the Cases 13: Diagnostic Hypothesis Generation 14: Refinement of Diagnostic Hypotheses 15: Use and Interpretation of Diagnostic Tests 16: Causal Reasoning 17: Diagnostic Verification 18: Therapeutic Decision Making 19: Examining Evidence 20: Cognitive Errors 21: Some Cognitive Concepts 22: Learning Clinical Problem Solving
Knowledge of risk factors may not improve management
Authors: J. Nash, P. Baragwanath, R. A Salaman, V. Banks, S. Bale, K. G Harding
Journal: BMJ (1994)

Pressure soresNot considered a priority by medical staff EDrrOR,-R K Vohra and C N McCollum's review of pressure sores is a timely reminder of the continuing silent epidemic of pressure sores both in hospital and in the community.'Pressure sores impose two main penalties, financial and human.The financial costs are high and result from additional treatment, a prolonged stay in hospital, and a further demand on clinic (nursing) time.Prevention of pressure sores is based on constant vigilance and early action, with awareness being the keynote of success.A colleague and I conducted a detailed survey with a semistructured questionnaire in a university teaching hospital; medical staff responded poorly to the questionnaire because pressure sores were not considered to be a priority.2Only about a quarter of medical staff routinely assessed patients with regard to their risk of pressure sores, though most nursing and therapy staff performed routine assessments.Hospital staff other than nursing staff were unaware of any protocols for assessing pres- sure sores.Most of the respondents thought that the cost of treating an inpatient with a pressure sore was less than £;1000; this indicates their unaware- ness of the true cost.It is prudent to apply low technology early rather than high technology at a later stage.If equipment is required it should be compatible with existing equipment, and unless costs are realistic the strategy is doomed to failure.
Pharmacoeconomic analysis of capecitabine for advanced gastric cancer in Taiwan
Authors: C. Chang, Y. Chao, J. Chen, L. Chen, C. Chuang, R. Hsieh, W. Hwang, L. Yang, F. de Reydet
Journal: Journal of Clinical Oncology (2008)

15576 Background: Capecitabine combined with cisplatin (XP) is a safe and effective alternative to intravenous 5-fluorouracil plus cisplatin (FP) in previously untreated patients with advanced and metastatic gastric cancer (AGC). The objective of this pharmacoeconomic analysis was to access the cost-effectiveness of XP versus FP for AGC treatment from Taiwan societal perspective. Methods: A cost-minimization analysis was undertaken by applying clinical outcomes and medical resource utilization (MRU) retrieved from phase III ML17032 study. Direct medical costs associated with trial-based MRU were based on Taiwan's National Health Insurance fee schedule for 2007. Costs associated with intravenous chemotherapy administration and adverse event (AE) management were estimated by an expert panel survey conducted among 12 oncologists. From a societal perspective, direct non-medical and indirect costs borne by patients, such as travel and time costs, were also considered. One-way sensitivity analyses were performed on key model parameters by varying the input values by ± 10%. Results: A trend toward superior progression-free survival was observed in XP arm (median 5.6 months for XP versus 5.0 for FP). Compared to FP, administration of XP required fewer consults per patient (5.2 for XP versus 22.8 for FP). Chemotherapy drug cost was higher (USD$1,712) in the XP arm; however, these cost increments were offset by differences of chemotherapy administration costs (USD$4,376) between two arms. AE profiles were similar and the costs associated with grade 3/4 AE management were slightly lower (USD$30) in the XP arm. Taking into account direct medical costs (chemotherapy administration and AE management), direct non- medical cost (travel), and indirect cost (time), XP was associated with a significant cost saving of USD$5,310 (NTD$172,197). XP remained cost-saving under one-way sensitivity analyses. Conclusions: Given the trend to superior efficacy, the significant cost savings, and the convenience of oral treatment, XP would be a dominant (less costly and more effective) regimen for AGC from the Taiwan societal perspective. Replacing FP by XP would not only reduce health care expenditures but also improve health outcomes in Taiwan. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration F. Hoffmann-La Roche AG, Roche Taiwan
Snoring is more strongly associated with chronic bronchitis in non-smokers
Authors: Ghassan Elsayed
Journal: Thorax (2008)

It has been suggested that patients with chronic bronchitis are more likely to snore during sleep. The authors studied 5015 people in Korea aged 40–69 years who all participated in a comprehensive health examination and on-site interview. Participants who reported symptoms suggesting chronic bronchitis or a previous diagnosis of chronic obstructive pulmonary disease who did not …
Bulimia nervosa in a Canadian community sample: prevalence and comparison of subgroups
Authors: P E Garfinkel, E Lin, P Goering, C Spegg, D S Goldbloom, S Kennedy, A S Kaplan, D B Woodside
Journal: American Journal of Psychiatry (1995)

Previous epidemiological studies of bulimia nervosa have generated differing estimates of the incidence and prevalence of the disorder. These differences are attributable, in part, to varying definitions of the illness and a range of methodologies. The authors sought to define the prevalence of bulimia nervosa in a nonclinical community sample, examine the clinical significance of DSM-III-R threshold criteria, and examine comorbidity.Subjects across Ontario (N = 8,116) were assessed with a structured interview, the World Health Organization Composite International Diagnostic Interview, with specific questions added for bulimia nervosa. Subjects who met DSM-III-R criteria for bulimia nervosa were compared with those who were missing only the frequency criterion (two or more binge-eating episodes per week for 3 months).In this sample, the lifetime prevalence of bulimia nervosa was 1.1% for female subjects and 0.1% for male subjects. The subjects with full- and partial-syndrome bulimia nervosa showed significant vulnerability for mood and anxiety disorders. Lifetime rates of alcohol dependence were high in the full-syndrome group. Rates of parental psychopathologies were high in both bulimic groups but tended to be higher in the subjects with full-syndrome bulimia nervosa. Both bulimic groups were significantly more likely to experience childhood sexual abuse than a normal female comparison group.This study confirms other prevalence estimates of bulimia nervosa and its comorbid diagnoses from studies that were based on sound methodologies. It also points to the arbitrary aspects of the frequency of binge eating as a diagnostic threshold criterion for the disorder.
Prophylactic melatonin significantly reduces Alzheimer’s neuropathology and associated cognitive deficits independent of antioxidant pathways in AβPPswe/PS1 mice
Authors: G. O’Neal-Moffitt, V. Delic, P. C. Bradshaw, J. Olcese
Journal: Molecular Neurodegeneration (2015)

Alzheimer's disease (AD) underlies dementia for millions of people worldwide, and its occurrence is set to double in the next 20 years. Currently, approved drugs for treating AD only marginally ameliorate cognitive deficits, and provide limited symptomatic relief, while newer substances under therapeutic development are potentially years away from benefiting patients. Melatonin (MEL) for insomnia has been proven safe with >15 years of over-the-counter access in the US. MEL exerts multiple complementary mechanisms of action against AD in animal models; thus it may be an excellent disease-modifying therapeutic. While presumed to provide neuroprotection via activation of known G-protein-coupled melatonin receptors (MTNRs), some data indicate MEL acts intracellularly to protect mitochondria and neurons by scavenging reactive oxygen species and reducing free radical formation. We examined whether genetic deletion of MTNRs abolishes MEL's neuroprotective actions in the AβPP(swe)/PSEN1dE9 mouse model of AD (2xAD). Beginning at 4 months of age, both AD and control mice either with or without both MTNRs were administered either MEL or vehicle in drinking water for 12 months.Behavioral and cognitive assessments of 15-month-old AD mice revealed receptor-dependent effects of MEL on spatial learning and memory (Barnes maze, Morris Water Maze), but receptor-independent neuroprotective actions of MEL on non-spatial cognitive performance (Novel Object Recognition Test). Similarly, amyloid plaque loads in hippocampus and frontal cortex, as well as plasma Aβ1-42 levels, were significantly reduced by MEL in a receptor-independent manner, in contrast to MEL's efficacy in reducing cortical antioxidant gene expression (Catalase, SOD1, Glutathione Peroxidase-1, Nrf2) only when receptors were present. Increased cytochrome c oxidase activity was seen in 16 mo AD mice as compared to non-AD control mice. This increase was completely prevented by MEL treatment of 2xAD/MTNR+ mice, but only partially prevented in 2xAD/MTNR- mice, consistent with mixed receptor-dependent and independent effects of MEL on this measure of mitochondrial function.These findings demonstrate that prophylactic MEL significantly reduces AD neuropathology and associated cognitive deficits in a manner that is independent of antioxidant pathways. Future identification of direct molecular targets for MEL action in the brain should open new vistas for development of better AD therapeutics.
Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force
Authors: Janelle M. Guirguis-Blake, Corinne V. Evans, Caitlyn A. Senger, Elizabeth A. O'Connor, Evelyn P. Whitlock
Journal: Annals of Internal Medicine (2016)

Background: Cardiovascular disease (CVD) is the leading cause of death in the United States. Purpose: To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations. Data Sources: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews. Study Selection: Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events. Data Extraction: Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second. Data Synthesis: Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10]). Limitation: Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses. Conclusion: The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit. Primary Funding Source: Agency for Healthcare Research and Quality.