tbuckley/cabot-search huggingface dataset:
Altered Na+/Ca2+-exchanger activity due to downregulation of Na+/K+-ATPase 2-isoform in heart failure
Authors: F. Swift, J. A. K. Birkeland, N. Tovsrud, U. H. Enger, J. M. Aronsen, W. E. Louch, I. Sjaastad, O. M. Sejersted
Journal: Cardiovascular Research (2008)

The Na+/K+-ATPase (NKA) α2-isoform is preferentially located in the t-tubules of cardiomyocytes and is functionally coupled to the Na+/Ca2+-exchanger (NCX) and Ca2+ regulation through intracellular Na+ concentration ([Na+]i). We hypothesized that downregulation of the NKA α2-isoform during congestive heart failure (CHF) disturbs the link between Na+ and Ca2+, and thus the control of cardiomyocyte contraction. NKA isoform and t-tubule distributions were studied using immunocytochemistry, confocal and electron microscopy in a post-infarction rat model of CHF. Sham-operated rats served as controls. NKA and NCX currents (INKA and INCX) were measured and α2-isoform current (INKA,α2) was separated from total INKA using 0.3 µM ouabain. Detubulation of cardiomyocytes was performed to assess the presence of α2-isoforms in the t-tubules. In CHF, the t-tubule network had a disorganized appearance in both isolated cardiomyocytes and fixed tissue. This was associated with altered expression patterns of NKA α1- and α2-isoforms. INKA,α2 density was reduced by 78% in CHF, in agreement with decreased protein expression (74%). When INKA,α2 was blocked in Sham cardiomyocytes, contractile parameters converged with those observed in CHF. In Sham, abrupt activation of INKA led to a decrease in INCX, presumably due to local depletion of [Na+]i in the vicinity of NCX. This decrease was smaller when the α2-isoform was downregulated (CHF) or inhibited (ouabain), indicating that the α2-isoform is necessary to modulate local [Na+]i close to NCX. Downregulation of the α2-isoform causes attenuated control of NCX activity in CHF, reducing its capability to extrude Ca2+ from cardiomyocytes.
Routes of Infection, Viremia, and Liver Disease in Blood Donors Found to Have Hepatitis C Virus Infection
Authors: Cathy Conry-Cantilena, Mark VanRaden, Joan Gibble, Jacqueline Melpolder, A. Obaid Shakil, Luis Viladomiu, Ling Cheung, Adrian DiBisceglie, Jay Hoofnagle, James W. Shih, Richard Kaslow, Paul Ness, Harvey J. Alter
Journal: New England Journal of Medicine (1996)

For many people infected with the hepatitis C virus (HCV), the route of exposure, risk of transmission, and severity of associated liver disease are unknown. We studied these variables in people who donated blood voluntarily.
Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.
Authors: B Jeremic, Y Shibamoto, L Acimovic, S Milisavljevic
Journal: Journal of Clinical Oncology (1997)

To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.
Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials
Authors: Dean Fergusson, Steve Doucette, Kathleen Cranley Glass, Stan Shapiro, David Healy, Paul Hebert, Brian Hutton
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts. <b>Design</b> Systematic review of randomised controlled trials. <b>Data sources</b> Medline and the Cochrane Collaboration9s register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group. <b>Selection of studies</b> Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week. <b>Results</b> Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42). <b>Discussion</b> Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.
AN INQUIRY INTO SOME MECHANICAL FACTORS IN THE PRODUCTION OF LYMPHOCYTOSIS
Authors: F. Peyton Rous
Journal: The Journal of Experimental Medicine (1908)

1. The lymph of the thoracic duct furnishes to the blood a larger proportion than is usually supposed of the lymphocytes in circulation. Gross variations in its output of such cells must affect very considerably the blood picture. 2. The quantity of lymphocytes supplied through the thoracic duct of the healthy dog remains practically constant from hour to hour, if the physiological conditions are not notably changed. Transient change in physiological conditions may alter the output of cells, but with the disappearance of this change the output tends to resume its previous rate. These facts indicate that the tissues producing lymphocytes are "set" at a rate of activity definite in the individual. 3. Muscular activity (struggle) produces a prompt increase in the output of lymphocytes through the thoracic duct. (a) This is assured by the presence of an increased number of cells per cubic millimeter of lymph, combined with an increase in the amount of lymph voided. (b) The lymphocyte-output may be tripled or quadrupled during a long-continued struggle. (c) Following prolonged struggle the output of lymphocytes is for a short time less than previous to the exertion. 4. The increased lymph-flow caused by a lymphagogue of the second class (glucose) brings with it increased output of lymphocytes through the thoracic duct. (a) The individual cubic millimeters of lymph are often poor in cells, during the rapid lymph-flow, yet the total number of elements transported is large. (b) The results with glucose support the theory of Ehrlich, that a rapidly appearing lymphocytosis may be produced through the flushing effect of increased lymph-flow. 5. A comparison of the effects of struggle with those of glucose demonstrates that in the former some factor besides increase in lymph-flow per se (Ehrlich) works to cause the large output of lymphocytes. The nature of this factor has not yet been determined. 6. The variations caused by muscular exertion and by increased lymph-flow in the number of lymphocytes coursing through the thoracic duct are so pronounced as to suggest that the total number of lymphocytes in circulation must be considerably influenced by them. Clinical findings by other observers indicate that this is true; and the clinical findings themselves become much simpler of interpretation. 7. The results in general prove the existence, reserved from circulation, of a large fund of lymphocytes, which is quickly yielded to the blood under certain physiological conditions.
Exercise and PGC-1α-Independent Synchronization of Type I Muscle Metabolism and Vasculature by ERRγ
Authors: Vihang A. Narkar, Weiwei Fan, Michael Downes, Ruth T. Yu, Johan W. Jonker, William A. Alaynick, Ester Banayo, Malith S. Karunasiri, Sabina Lorca, Ronald M. Evans
Journal: Cell Metabolism (2011)
Age-Dependent Profile of Left-Sided Infective Endocarditis
Authors: Javier López, Ana Revilla, Isidre Vilacosta, Teresa Sevilla, Eduardo Villacorta, Cristina Sarriá, Eduardo Pozo, María Jesús Rollán, Itziar Gómez, Pedro Mota, José Alberto San Román
Journal: Circulation (2010)

The influence of age on the main epidemiological, clinical, echocardiographic, microbiological, and prognostic features of patients with infective endocarditis remains unknown. We present the series with the largest numbers and range of ages of subjects to date that analyzes the influence of age on the main characteristics of patients with isolated left-sided infective endocarditis. Furthermore, this series is the first one in which patients have been distributed according to age quartile.A total of 600 episodes of left-sided endocarditis consecutively diagnosed in 3 tertiary centers were stratified into age-specific quartiles and 107 variables compared between the different groups. With increasing age, the percentage of women, previous heart disease, predisposing disease (diabetes mellitus and cancer), and infection by enterococci and Streptococcus bovis also increased. Valvular insufficiency and perforation and Staphylococcus aureus infection were more common in younger patients. The therapeutic approach differed depending on patient age because of the growing proportion of older patients who only received medical treatment. Clinical course and hospital prognosis were worse in the older patients because of increased surgical mortality among them.Increasing age is associated with less valvular impairment (insufficiency and perforation), a more favorable microbiological profile, and increased surgical mortality among adults with left-sided infective endocarditis.
Alignment of new tuberculosis drug regimens and drug susceptibility testing: a framework for action
Authors: William A Wells, Catharina C Boehme, Frank GJ Cobelens, Colleen Daniels, David Dowdy, Elizabeth Gardiner, Jan Gheuens, Peter Kim, Michael E Kimerling, Barry Kreiswirth, Christian Lienhardt, Khisi Mdluli, Madhukar Pai, Mark D Perkins, Trevor Peter, Matteo Zignol, Alimuddin Zumla, Marco Schito
Journal: The Lancet Infectious Diseases (2013)
Under-reporting of conflicts of interest among trialists: a cross-sectional study
Authors: Kristine Rasmussen, Jeppe Schroll, Peter C Gøtzsche, Andreas Lundh
Journal: Journal of the Royal Society of Medicine (2014)

To determine the prevalence of conflicts of interest (COIs) among Danish physicians who are authors of clinical drug trial reports and determine the extent of undisclosed COIs in trial publications.Cross-sectional study.The 100 most recent drug trial reports with at least one Danish non-industry employed physician author published in a journal adhering to the International Committee of Medical Journal Editors' (ICMJE) manuscript guidelines. For each article, two observers independently extracted trial characteristics and the authors' COIs. Disclosed COIs were compared to what was registered on the Danish Health and Medicines Authority's public disclosure list.Trial authors who are Danish physicians.Number of disclosed and undisclosed COIs.One observer screened 928 articles and two observers assessed 120 articles for eligibility. The 100 included trials were published from February 2011 to May 2013 and included 318 Danish non-industry employed authors. Eighty-six of the 318 authors (27%) reported one or more COIs in the journal article. We found undisclosed COIs for 40 of 318 authors (13%) related to the trial sponsor or manufacturer of trial drugs. Seventy-nine of 318 authors (25%) had undisclosed COIs related to competing companies manufacturing drugs for the same indication and 136 (43%) had undisclosed COIs with any drug manufacturer.Almost half of all authors had undisclosed COIs in clinical trials reported in journals adhering to the International Committee of Medical Journal Editors' manuscript guidelines. Self-declared COIs cannot be trusted, but public registries may assist editors in ensuring that more COIs are being reported.
Primary diffuse alveolar septal amyloidosis with multiple cysts and calcification
Authors: S. Ohdama, S. Akagawa, O. Matsubara, Y. Yoshizawa
Journal: European Respiratory Journal (1996)

We report an extremely rare case of primary diffuse alveolar septal amyloidosis associated with multiple cysts and calcification. Development of multiple cysts may have resulted from fragile alveolar walls, as a consequence of amyloid deposition both on alveolar walls and around capillaries.
Contributions from the<i>European Respiratory Monograph</i>: a new series in the journal
Authors: M. Decramer, A. Rossi
Journal: European Respiratory Journal (2001)

The European Respiratory Monograph is an educational publication of the European Respiratory Society that started in 1995. Since 1995, 15 Monographs have been published on various topics including: Carcinoma of the lung, AIDS and the lung, Pneumonia, Tuberculosis, New diagnostic techniques in paediatric respiratory medicine, Clinical exercise testing, Management of chronic obstructive pulmonary disease, Mechanical ventilation from intensive care to home care, Pulmonary endoscopy and biopsy techniques, Respiratory disorders during sleep, Occupational lung disease, Respiratory mechanics, Pulmonary rehabilitation, Interstitial lung diseases, and Respiratory epidemiology in Europe. An average of three Monographs per annum have been published for the last five years. These Monographs had 8–26 chapters and 22–55 authors per issue.

The Monographs provide an excellent state-of-the-art overview of a particular disease, a particular diagnostic or therapeutic technique or a particular field of interest. They are primarily targeted at residents in training and in that sense they are teaching publications, but also established chest physicians as well as academic physicians might find that the publications provide them with …
Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation
Authors: Antoine Froidure, Olivier Vandenplas, Vinciane D'Alpaos, Geneviève Evrard, Charles Pilette
Journal: Thorax (2015)

<h3>Background</h3> The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown. <h3>Objectives</h3> We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma after allergen avoidance. <h3>Methods</h3> We recruited 32 patients with occupational asthma to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterise blood type 1 mDCs, and their functionality was studied in coculture with allogeneic CD4<sup>+</sup> T cells from controls. <h3>Results</h3> At follow-up, 11/32 patients (34%) were characterised by the absence of symptoms and non-specific bronchial hyper-responsiveness to histamine and were considered to be cured. When compared with cured patients, mDCs from patients with persistent disease increased the production of interleukin (IL) 5 and IL-13 by CD4<sup>+</sup> T cells, and upregulated programmed death ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade. <h3>Conclusions</h3> This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by dendritic cells is flexible and partly mediated by PD-L2.
MicroRNA‐494 within an oncogenic microRNA megacluster regulates G <sub>1</sub> /S transition in liver tumorigenesis through suppression of mutated in colorectal cancer
Authors: Lionel Lim, Asha Balakrishnan, Noelle Huskey, Kirk D. Jones, Mona Jodari, Raymond Ng, Guisheng Song, Jesse Riordan, Brittany Anderton, Siu‐Tim Cheung, Holger Willenbring, Adam Dupuy, Xin Chen, David Brown, Aaron N. Chang, Andrei Goga
Journal: Hepatology (2013)

Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver's unique affinity for small nucleic acids, miRNA-based therapy has been proposed in the treatment of liver disease. Thus, there is an urgent need to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCCs. We identified an up-regulated miRNA megacluster comprised of 53 miRNAs on mouse chromosome 12qF1 (human homolog 14q32). This miRNA megacluster is up-regulated in all three transgenic liver models and in a subset of human HCCs. An unbiased functional analysis of all miRNAs within this cluster was performed. We found that miR-494 is overexpressed in human HCC and aids in transformation by regulating the G1 /S cell cycle transition through targeting of the Mutated in Colorectal Cancer tumor suppressor. miR-494 inhibition in human HCC cell lines decreases cellular transformation, and anti-miR-494 treatment of primary MYC-driven liver tumor formation significantly diminishes tumor size.Our findings identify a new therapeutic target (miR-494) for the treatment of HCC.
NHS is told it must play its part in tackling climate change
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Clinicians have been urged to play their part in helping the NHS to reduce its carbon footprint.

The NHS emits one million tonnes of carbon a year as one of the largest and most resource hungry organisations in the world, says a report published by the independent think tank the New Economics Foundation.

The report, produced for the NHS Confederation (the body that represents NHS organisations), says that the NHS spends around £400m (€600m; $800m) every year on energy and that it must take steps to try to reduce the effect this is having on the environment.

Every year, says …
Inhibition of Phosphatidylinositol 3-Kinase Destabilizes Mycn Protein and Blocks Malignant Progression in Neuroblastoma
Authors: Louis Chesler, Chris Schlieve, David D. Goldenberg, Anna Kenney, Grace Kim, Alex McMillan, Katherine K. Matthay, David Rowitch, William A. Weiss
Journal: Cancer Research (2006)

Abstract Amplification of MYCN occurs commonly in neuroblastoma. We report that phosphatidylinositol 3-kinase (PI3K) inhibition in murine neuroblastoma (driven by a tyrosine hydroxylase-MYCN transgene) led to decreased tumor mass and decreased levels of Mycn protein without affecting levels of MYCN mRNA. Consistent with these observations, PI3K inhibition in MYCN-amplified human neuroblastoma cell lines resulted in decreased levels of Mycn protein without affecting levels of MYCN mRNA and caused decreased proliferation and increased apoptosis. To clarify the importance of Mycn as a target of broad-spectrum PI3K inhibitors, we transduced wild-type N-myc and N-myc mutants lacking glycogen synthase kinase 3β phosphorylation sites into human neuroblastoma cells with no endogenous expression of myc. In contrast to wild-type N-myc, the phosphorylation-defective mutant proteins were stabilized and were resistant to the antiproliferative effects of PI3K inhibition. Our results show the importance of Mycn as a therapeutic target in established tumors in vivo, offer a mechanistic rationale to test PI3K inhibitors in MYCN-amplified neuroblastoma, and represent a therapeutic approach applicable to a broad range of cancers in which transcription factors are stabilized through a PI3K-dependent mechanism. (Cancer Res 2006; 66(16): 8139-46)
Domestic Partnership Benefits at Medical Universities
Authors: Katherine A. O'Hanlan
Journal: JAMA (1999)

S brutal murder of Wyoming college student Matthew Shepard brought forth recognition that despite much greater acceptance of gay and lesbian people than in recent history, antihomosexual discrimination marked by occasional violence remains a divisive fixture in the American social landscape. 1 Certainly conditions for gay and lesbian people have improved, especially within the medical profession.A moderate number of gay and lesbian medical students and physicians are now formally protected by antidiscrimination clauses in their academic and working lives.Many gay and lesbian physicians achieve high degrees of professional success, even after having disclosed their orientation to select colleagues and employers.In this issue, Jason Schneider and Saul Levin, MD, trace the American Medical Association's growing acceptance of gay and lesbian visibility within its own ranks over the past 2 decades.Kate O'Hanlan, MD, follows with a discussion of her experiences over the past 10 years in successfully advocating for domestic partner benefits at Albert Einstein College of Medicine and Stanford University.Yet despite successes in professional representation and employment status, surveys have documented that many admissions officers and residency directors are less enthusiastic about gay and lesbian candidates than heterosexual candidates, and that physicians who disclose a nonheterosexual orientation to colleagues face the potential loss of referrals and privileges. 2,3A nationwide survey of women physicians by researchers at Emory University provides new evidence that lesbian physicians do in fact experience harassment at a greater prevalence than their heterosexual counterparts.From the patient's perspective, sexual orientation may expose one to specific health risks.Gary Remafedi, MD, provides a sobering view of the most catastrophic result of antihomosexual discrimination in his review of studies linking adolescent suicide to gay or lesbian sexual orientation.Suicide is among the most dangerous health risks of all to gay and lesbian teenagers and the most unrelentingly tragic.Finally, this month's MSJAMA online features an interview with and new poetry by Rafael Campo, MD, who has made a point of addressing gay issues and the patient-physician relationship in his writing.Campo inspires readers with his injunctions to remain human as a first priority-and thereby to experience empathy with others.One may hope, as Campo's writing and these articles suggest, that these special insights of the medical profession have the potential to better a society still struggling with its prejudices.