tbuckley/cabot-search huggingface dataset:
Risk of suicide and related adverse outcomes after exposure to a suicide prevention programme in the US Air Force: cohort study
Authors: Kerry L Knox, David A Litts, G Wayne Talcott, Jill Catalano Feig, Eric D Caine
Journal: BMJ (2003)

To evaluate the impact of the US Air Force suicide prevention programme on risk of suicide and other outcomes that share underlying risk factors.Cohort study with quasi-experimental design and analysis of cohorts before (1990-6) and after (1997-2002) the intervention.5,260,292 US Air Force personnel (around 84% were men).A multilayered intervention targeted at reducing risk factors and enhancing factors considered protective. The intervention consisted of removing the stigma of seeking help for a mental health or psychosocial problem, enhancing understanding of mental health, and changing policies and social norms.Relative risk reductions (the prevented fraction) for suicide and other outcomes hypothesised to be sensitive to broadly based community prevention efforts, (family violence, accidental death, homicide). Additional outcomes not exclusively associated with suicide were included because of the comprehensiveness of the programme.Implementation of the programme was associated with a sustained decline in the rate of suicide and other adverse outcomes. A 33% relative risk reduction was observed for suicide after the intervention; reductions for other outcomes ranged from 18-54%.A systemic intervention aimed at changing social norms about seeking help and incorporating training in suicide prevention has a considerable impact on promotion of mental health. The impact on adverse outcomes in addition to suicide strengthens the conclusion that the programme was responsible for these reductions in risk.
Women's respiratory vulnerability to tobacco smoking
Authors: R Liard, B Leynaert, F Neukirch, J Bousquet
Journal: European Respiratory Journal (1998)

We thank Liard, Leynaert, Neukirch and Bousquet for their comments regarding our recent paper [1] and for supplying additional data.In addition to our results regarding admission to hospital for chronic obstructive pulmonary disease (COPD), we have found that female smokers have a higher relative mortality risk from respiratory disease than male smokers, compared to never-smokers of the corresponding gender [2].
Distinct Cutaneous Manifestations and Cold-Induced Leukocyte Activation Associated With<i>PLCG2</i>Mutations
Authors: Oyinade M. Aderibigbe, Debra Long Priel, Chyi-Chia Richard Lee, Michael J. Ombrello, Vimal H. Prajapati, Marilyn G. Liang, Jonathan J. Lyons, Douglas B. Kuhns, Edward W. Cowen, Joshua D. Milner
Journal: JAMA Dermatology (2015)

<h3>Importance</h3> <i>PLCG2</i>-associated antibody deficiency and immune dysregulation (PLAID) is a newly characterized immunodeficiency syndrome associated with distinct cutaneous features. Awareness of the cutaneous skin findings associated with PLAID may facilitate diagnosis and improve patient care. <h3>Objectives</h3> To characterize the cutaneous manifestations of PLAID and identify potential cellular mechanisms of the disease. <h3>Design, Setting, and Participants</h3> In this retrospective analysis of patients with PLAID and PLAID-like disease evaluated at the National Institutes of Health from January 1, 2005, through December 31, 2014, patients with deletions in<i>PLCG2</i>leading to PLAID and patients with PLAID-like disease for whom a PLAID mutation was not identified were studied. <h3>Main Outcomes and Measures</h3> Characterization of cutaneous manifestations of PLAID and PLAID-like disease and analysis of PLAID immune cell activation. <h3>Results</h3> Among 36 patients with PLAID and PLAID-like phenotypes, all of whom had evaporative cold urticaria, 8 patients had a history of unique neonatal-onset ulcerative and cutaneous lesions in cold-sensitive regions of the body. Granulomatous skin lesions sparing warm regions (eg, flexural surfaces and skinfolds) were identified in 4 patients. Neutrophils and monocytes from patients with PLAID exhibited enhanced baseline activation in vitro, which was potentiated by ambient temperature exposure. <h3>Conclusions and Relevance</h3> Collectively, these findings suggest that early identification of neonatal lesions may help in the diagnosis of PLAID and that leukocyte hyperactivation may underlie cutaneous lesions in patients with PLAID. Further characterization of mechanisms underlying leukocyte hyperactivation may contribute to the fundamental understanding of granuloma formation.
Heme Oxygenase-1 Expression in Macrophages Plays a Beneficial Role in Atherosclerosis
Authors: Luz D. Orozco, Matthias H. Kapturczak, Berenice Barajas, Xuping Wang, Michael M. Weinstein, Jack Wong, Jessy Deshane, Subhashini Bolisetty, Zory Shaposhnik, Diana M. Shih, Anupam Agarwal, Aldons J. Lusis, Jesus A. Araujo
Journal: Circulation Research (2007)

Heme oxygenase (HO-1) is the rate-limiting enzyme in the catabolism of heme, which leads to the generation of biliverdin, iron, and carbon monoxide. It has been shown to have important antioxidant and antiinflammatory properties that result in a vascular antiatherogenic effect. To determine whether HO-1 expression in macrophages constitutes a significant component of the protective role in atherosclerosis, we evaluated the effect of decreased or absent HO-1 expression in peritoneal macrophages on oxidative stress and inflammation in vitro, and the effect of complete deficiency of HO-1 expression in macrophages in atherosclerotic lesion formation in vivo. We found that compared with HO-1 +/+ controls, peritoneal macrophages from HO-1 −/− and HO-1 +/− mice exhibited (1) increased reactive oxygen species (ROS) generation, (2) increased proinflammatory cytokines such as monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), and (3) increased foam cell formation when treated with oxLDL, attributable in part to increased expression of scavenger receptor A (SR-A). Bone marrow transplantation experiments performed in lethally irradiated LDL-R null female mice, reconstituted with bone marrow from HO-1 −/− versus HO-1 +/+ mice, revealed that HO-1 −/− reconstituted animals exhibited atherosclerotic lesions with a greater macrophage content as evaluated by immunohistochemistry and planimetric assessment. We conclude that HO-1 expression in macrophages constitutes an important component of the antiatherogenic effect by increasing antioxidant protection and decreasing the inflammatory component of atherosclerotic lesions.
Left Ventricular Size and Function and Heart Size in the Year Following Myocardial Infarction
Authors: BOLLING J. FEILD, RICHARD O. RUSSELL, ROGER E. MORASKI, BENIGNO SOTO, WILLIAM P. HOOD, JOHN A. BURDESHAW, MCKAMY SMITH, BRIAN J. MAURER, CHARLES E. RACKLEY
Journal: Circulation (1974)

Interrelationships among left ventricular (LV) size, LV function, and heart size were investigated in 49 patients studied 2-12 months after myocardial infarction. LV end-diastolic volume (EDV) and ejection fraction (EF) were determined by biplane ventriculography. Heart size was estimated from chest films by the cardiothoracic ratio (CTR) and cardiac volume (CV) methods. Ventricular function (i.e., EF) was related to chamber size (i.e., EDV), but the correlation coefficient was not high ( r = 0.74); thus, chamber size was not an accurate predictor of EF. Because of the close linear relation that exists between LV end-systolic volume and EDV ( r = 0.98), a hyperbola describes the relation between EF and EDV. In general, EF was depressed (&lt;0.50) when EDV exceeded 70 ml/m 2 , was &lt;0.35 when EDV exceeded upper normal limits (110 ml/m 2 ), and was &lt;0.25 with chamber size &gt;150 ml/m 2 . Thus relatively small chamber size (&lt;150 ml/m 2 ) was associated with a wide range in ventricular function, while large chamber size was associated with severe dysfunction (EF &lt; 0.30). By either heart size method, cardiomegaly (CTR &gt; 0.50 or CV &gt; 540 ml/m 2 ) was not found consistently until EDV exceeded 150 ml/m 2 . Hence normal heart size was often associated with moderate EF depression (0.49-0.30), while cardiomegaly was often associated with severe dysfunction. Clinical heart failure (CHF) was usually accompanied by EF &lt; 0.30, but chamber size ranged from 101 to 331 ml/m 2 . Primarily because of this variation in chamber size, both normal heart size and cardiomegaly were at times associated with CHF. The poor correlations of EF with CTR ( r = –0.43) and CV ( r = –0.52) preclude use of the heart size indices as accurate predictors of LV function. When the data were analyzed according to the presence or absence of cardiomegaly, the following generalizations could be made regardless of the heart size method used. Cardiomegaly was a reasonable indicator of postinfarction LV function, being associated with depressed function and often with CHF. However normal heart size was associated with either normal LV function, or commonly, with depressed function, often not clinically apparent.
Human Monocyte-Derived Dendritic Cells Pulsed with Wild-Type p53 Protein Efficiently Induce CTLs against p53 Overexpressing Human Cancer Cells
Authors: Naoyuki Tokunaga, Takayoshi Murakami, Yoshikatsu Endo, Masahiko Nishizaki, Shunsuke Kagawa, Noriaki Tanaka, Toshiyoshi Fujiwara
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Dendritic cells are the most potent antigen-presenting cells for initiating cellular immune responses. Dendritic cells are attractive immunoregulatory cells for cancer immunotherapy, and their efficacy has been investigated in clinical trials. The tumor suppressor gene p53 is pivotal in the regulation of apoptosis, and p53-based immunization is an attractive approach to cancer immunotherapy because of the accumulation of p53 protein in malignant but not in normal cells. It has been shown that dendritic cells transduced with an adenoviral wild-type p53 (wt-p53) construct mediate the antitumor immune responses against p53-overexpressing tumor cells. We examined whether monocyte-derived human dendritic cells pulsed with the purified full-length wt-p53 protein were also capable of inducing the specific antitumor responses against p53-overexpressing tumors in vitro. Experimental Design: Immature dendritic cells generated in the presence of interleukin-4 and granulocyte/macrophage colony-stimulating factor from monocytes of HLA-A2- or HLA-A24-positive healthy individuals were pulsed with the purified p53 protein. Uptake of p53 protein by human dendritic cells was assessed by Western blotting and immunohistochemical staining using anti-p53 antibody. Induction of p53-specific CTL response was also evaluated by the cytotoxic assay against p53-overexpressing human tumor cells. Results: Both Western blot and immunohistochemical analysis showed the accumulation of p53 protein in human immature dendritic cells. T cells obtained from HLA-A2- or HLA-A24-positive healthy donors were stimulated twice with p53 protein-pulsed dendritic cells and then applied to the cytotoxicity assay against p53-overexpressing target cells. The CTL activity was specific for p53-overexpressing tumor cells and MHC class I restricted. Moreover, the CTL activity generated by p53 protein-pulsed dendritic cells was nearly identical with that induced by adenoviral wt-p53-transduced dendritic cells. Conclusions: Our results indicate that monocyte-derived human dendritic cells pulsed with the wt-p53 protein could induce the specific antitumor effect against p53-overexpressing tumors and that this in vitro model offers a new and more simple approach to the development of p53-based immunotherapy.
Variation in Mutation Rate and Polymorphism Among Mitochondrial Genes of Silene vulgaris
Authors: C. M. Barr, S. R. Keller, P. K. Ingvarsson, D. B. Sloan, D. R. Taylor
Journal: Molecular Biology and Evolution (2007)

The prevailing wisdom of the plant mitochondrial genome is that it has very low substitution rates, thus it is generally assumed that nucleotide diversity within species will also be low. However, recent evidence suggests plant mitochondrial genes may harbor variable and sometimes high levels of within-species polymorphism, a result attributed to variance in the influence of selection. However, insufficient attention has been paid to the effect of among-gene variation in mutation rate on varying levels of polymorphism across loci. We measured levels of polymorphism in seven mitochondrial gene regions across a geographically wide sample of the plant Silene vulgaris to investigate whether individual mitochondrial genes accumulate polymorphisms equally. We found that genes vary significantly in polymorphism. Tests based on coalescence theory show that the genes vary significantly in their scaled mutation rate, which, in the absence of differences among genes in effective population size, suggests these genes vary in their underlying mutation rate. Further evidence that among-gene variance in polymorphism is due to variation in the underlying mutation rate comes from a significant positive relationship between the number of segregating sites and silent site divergence from an outgroup. Contrary to recent studies, we found unconvincing evidence of recombination in the mitochondrial genome, and generally confirm the standard model of plant mitochondria characterized by low substitution rates and no recombination. We also show no evidence of significant variation in the strength or direction of selection among genes; this result may be expected if there is no recombination. The present study provides some of the most thorough data on plant mitochondrial polymorphism, and provides compelling evidence for mutation rate variation among genes. The study also demonstrates the difficulty in establishing a null model of mitochondrial genome polymorphism, and thus the difficulty, in the absence of a comparative approach, in testing the assumption that low substitution rates in plant mitochondria lead to low polymorphism.
Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study
Authors: Marie-Christine Durand, Raphaël Porcher, David Orlikowski, Jérôme Aboab, Christian Devaux, Bernard Clair, Djillali Annane, Jean-Louis Gaillard, Frédéric Lofaso, Jean-Claude Raphael, Tarek Sharshar
Journal: The Lancet Neurology (2006)
Low-Fat Dietary Pattern and Weight Change Over 7 Years
Authors: Barbara V. Howard, JoAnn E. Manson, Marcia L. Stefanick, Shirley A. Beresford, Gail Frank, Bobette Jones, Rebecca J. Rodabough, Linda Snetselaar, Cynthia Thomson, Lesley Tinker, Mara Vitolins, Ross Prentice
Journal: JAMA (2006)

Obesity in the United States has increased dramatically during the past several decades. There is debate about optimum calorie balance for prevention of weight gain, and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed, in part, to low-fat, high-carbohydrate diets.To report data on body weight in a long-term, low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components.Randomized intervention trial of 48,835 postmenopausal women in the United States who were of diverse backgrounds and ethnicities and participated in the Women's Health Initiative Dietary Modification Trial; 40% (19,541) were randomized to the intervention and 60% (29,294) to a control group. Study enrollment was between 1993 and 1998, and this analysis includes a mean follow-up of 7.5 years (through August 31, 2004).The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable, fruit, and grain consumption and did not include weight loss or caloric restriction goals. The control group received diet-related education materials.Change in body weight from baseline to follow-up.Women in the intervention group lost weight in the first year (mean of 2.2 kg, P<.001) and maintained lower weight than control women during an average 7.5 years of follow-up (difference, 1.9 kg, P<.001 at 1 year and 0.4 kg, P = .01 at 7.5 years). No tendency toward weight gain was observed in intervention group women overall or when stratified by age, ethnicity, or body mass index. Weight loss was greatest among women in either group who decreased their percentage of energy from fat. A similar but lesser trend was observed with increases in vegetable and fruit servings, and a nonsignificant trend toward weight loss occurred with increasing intake of fiber.A low-fat eating pattern does not result in weight gain in postmenopausal women. Clinical Trial Registration ClinicalTrials.gov, NCT00000611.
Cure of Fisher Rats Bearing Radioresistant F98 Glioma Treated with <b> <i>cis</i> </b>-Platinum and Irradiated with Monochromatic Synchrotron X-Rays
Authors: Marie-Claude Biston, Aurélie Joubert, Jean-François Adam, Hélène Elleaume, Sylvain Bohic, Anne-Marie Charvet, François Estève, Nicolas Foray, Jacques Balosso
Journal: Cancer Research (2004)

Abstract High-grade gliomas are usually of poor prognosis, and conventional radiotherapy, even combined with chemotherapy, still fails to improve the survival of patients. Here, we propose an innovative therapeutic approach combining synchrotron radiation with cis-diamminedichloroplatinum (II) (CDDP). As suggested previously, monochromatic synchrotron irradiation of CDDP at 78.8 keV, just above the 78.4 keV platinum absorption K-edge, leads to an enhanced photoelectric effect and an increased local toxicity. To select a particular radiation energy that could provide supra-additive effect, we used pulsed-field gel electrophoresis to assess yields of DNA double-strand breaks induced in rat F98 glioma cells after CDDP treatment combined with synchrotron X-rays. Thereafter, intracerebral CDDP injection combined with synchrotron X-rays was applied to Fisher rats bearing F98 glioma. CDDP concentrations were mapped by synchrotron X-ray microfluorescence. An extra number of more slowly repaired double strand breaks were observed when irradiating CDDP-treated F98 cells at 78.8 keV. In vivo treatments were then performed with different radiation doses and CDDP concentrations. All cell inoculations in rat brain resulted in tumor development, and tumor presence was controlled by computed tomography. Among all of the conditions tested, the combination of 3 μg of CDDP with 15 Gy resulted in the largest median survival time (206 days). After 1 year, about 34% of treated rats were still alive. This preclinical finding, validated by molecular analysis, represents the most protracted survival reported with this radioresistant glioma model and demonstrates the interest in powerful monochromatic X-ray sources as new tools for cancer treatments.
Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma
Authors: J. Maloney, S. Durham, D. Skoner, R. Dahl, A. Bufe, D. Bernstein, K. Murphy, S. Waserman, G. Berman, M. White, A. Kaur, H. Nolte
Journal: Allergy (2014)

Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with/without conjunctivitis (AR/C), AE frequencies were determined in adults and children with and without reported asthma.Data from randomized, double-blind, placebo-controlled trials of Timothy grass SLIT-tablet MK-7243 (2800 BAU/75 000 SQ-T, Merck/ALK-Abelló) were pooled for post hoc analyses. Subjects with uncontrolled and severe asthma were excluded from the trials. Frequencies for treatment-emergent AEs (TEAEs), local allergic swelling (mouth or throat), systemic allergic reactions, and asthma-related treatment-related AEs (TRAEs) were calculated.Among adults (n = 3314) and children (n = 881), 24% and 31%, respectively, had reported asthma. No serious local allergic swellings or serious systemic allergic reactions occurred in subjects with asthma treated with SLIT-tablet. There was no evidence of increased TEAEs, systemic allergic reactions, or severe local allergic swellings in adults or children with asthma treated with grass SLIT-tablet versus subjects without asthma in or outside of pollen season. There were 6/120 asthma-related TRAEs assessed as severe with grass SLIT-tablet and 2/60 with placebo, without a consistent trend among subjects with and without asthma (5 and 3 events, respectively).In the AR/C subjects with reported well-controlled mild asthma included in these studies, grass SLIT-tablet did not increase TEAE frequency, severe local allergic swelling, or systemic allergic reactions versus subjects without asthma. There was no indication that treatment led to acute asthma worsening.
Biomarker-based adaptive trials for patients with glioblastoma--lessons from I-SPY 2
Authors: B. M. Alexander, P. Y. Wen, L. Trippa, D. A. Reardon, W.-K. A. Yung, G. Parmigiani, D. A. Berry
Journal: Neuro-Oncology (2013)

The traditional clinical trials infrastructure may not be ideally suited to evaluate the numerous therapeutic hypotheses that result from the increasing number of available targeted agents combined with the various methodologies to molecularly subclassify patients with glioblastoma. Additionally, results from smaller screening studies are rarely translated to successful larger confirmatory studies, potentially related to a lack of efficient control arms or the use of unvalidated surrogate endpoints. Streamlining clinical trials and providing a flexible infrastructure for biomarker development is clearly needed for patients with glioblastoma. The experience developing and implementing the I-SPY studies in breast cancer may serve as a guide to developing such trials in neuro-oncology.
The health impact of pemphigus vulgaris and pemphigus foliaceus assessed using the Medical Outcomes Study 36-item short form health survey questionnaire
Authors: S. Tabolli, A. Mozzetta, V. Antinone, S. Alfani, G. Cianchini, D. Abeni
Journal: British Journal of Dermatology (2008)

Pemphigus vulgaris and pemphigus foliaceus are rare, potentially life-threatening, autoimmune disorders characterized by antibodies to epidermal adhesion molecules. Clinical characteristics are painful chronic erosions of mucous membranes and of the skin. There are only few published studies on the impact of the disease on the health status (HS) of patients with these conditions.To assess the impact of disease on the HS of patients with pemphigus.Fifty-eight patients enrolled at the Bullous Skin Diseases Unit of IDI-IRCCS in the period January-June 2006 were assessed for their HS using the Medical Outcomes Study 36-item short form health survey (SF-36) questionnaire and for anxiety and depression using the Institute for Personality and Ability Testing questionnaires.A compromised HS on both the physical and the psychosocial scales was observed, similar to other chronic dermatological diseases such as psoriasis. Patients with anxiety had severe disease as measured by the Physician's Global Assessment and the degree of mucocutaneous involvement, as well as those with a more recent disease onset. A better HS was observed in patients whose clinical condition was rated as nonsevere, and also in patients with pemphigus foliaceus. In pemphigus vulgaris, antidesmoglein 3 antibody levels directly correlated with clinical severity and with lower SF-36 scores.HS evaluated with the SF-36 can be a very useful additional outcome criterion in clinical studies with pemphigus. The management of the disease must take into account its impact on various aspects of life of the patient.