tbuckley/cabot-search huggingface dataset:
Organoids Help Uncover Possible Mechanisms of Autism
Authors: Tracy Hampton
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia
Authors: Jessica Y. Islam, Roberta L. Keller, Judy L. Aschner, Tina V. Hartert, Paul E. Moore
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease associated with premature birth that primarily affects infants born at less than 28 weeks' gestational age. BPD is the most common serious complication experienced by premature infants, with more than 8,000 newly diagnosed infants annually in the United States alone. In light of the increasing numbers of preterm survivors with BPD, improving the current state of knowledge of long-term respiratory morbidity for infants with BPD is a priority. We undertook a comprehensive review of the published literature to analyze and consolidate current knowledge of the effects of BPD that are recognized at specific stages of life, including infancy, childhood, and adulthood. In this review, we discuss both the short-term and long-term respiratory outcomes of individuals diagnosed as infants with the disease and highlight the gaps in knowledge needed to improve early and lifelong management of these patients.
Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids
Authors: Andrew D. Southam, Farhat L. Khanim, Rachel E. Hayden, Julia K. Constantinou, Katarzyna M. Koczula, Robert H. Michell, Mark R. Viant, Mark T. Drayson, Chris M. Bunce
Journal: Cancer Research (2015)

Abstract The redeployed drug combination of bezafibrate and medroxyprogesterone acetate (designated BaP) has potent in vivo anticancer activity in acute myelogenous leukemia (AML) and endemic Burkitt lymphoma (eBL) patients; however, its mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis is a hallmark of many cancers and that these drugs can affect lipid metabolism, we hypothesized that BaP exerts anticancer effects by disrupting lipogenesis. We applied mass spectrometry–based lipidomics and gene and protein expression measurements of key lipogenic enzymes [acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and stearoyl CoA desaturase 1 (SCD1)] to AML and eBL cell lines treated with BaP. BaP treatment decreased fatty acid and phospholipid biosynthesis from 13C D-glucose. The proportion of phospholipid species with saturated and monounsaturated acyl chains was also decreased after treatment, whereas those with polyunsaturated chains increased. BaP decreased SCD1 protein levels in each cell line (0.46- to 0.62-fold; P &amp;lt; 0.023) and decreased FASN protein levels across all cell lines (0.87-fold decrease; P = 1.7 × 10−4). Changes to ACC1 protein levels were mostly insignificant. Supplementation with the SCD1 enzymatic product, oleate, rescued AML and e-BL cells from BaP cell killing and decreased levels of BaP-induced reactive oxygen species, whereas supplementation with the SCD1 substrate (and FASN product), palmitate, did not rescue cells. In conclusion, these data suggest that the critical anticancer actions of BaP are decreases in SCD1 levels and monounsaturated fatty acid synthesis. To our knowledge, this is the first time that clinically available antileukemic and antilymphoma drugs targeting SCD1 have been reported. Cancer Res; 75(12); 2530–40. ©2015 AACR.
Vital Capacity Reservoir and Online Measurement of Childhood Nitrosopnea Are Linearly Related
Authors: ROBERT G. CANADY, THOMAS PLATTS-MILLS, ANDREW MURPHY, ROY JOHANNESEN, BENJAMIN GASTON
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Hypernitrosopnea, a robust marker for childhood asthma, is measured reproducibly in mixed vital capacity (VC) expirates. Recent guidelines for measurement of expired nitric oxide (NO) in adults have favored use of an online (OL), flow-dependent technique. We compared VC and OL NO measurements in 14 asthmatic and 11 control children 5 through 18 yr of age. After spirometry, subjects breathed both into an open-ended reservoir (20 cm H2O resistance) and into a tedlar bag (VC maneuver). End-expiratory pressure > 5 cm H2O was continuously maintained during VC measurements, and the velum remained shut. Eight additional children (24% of total number of subjects) were unable reproducibly to perform the OL measurement at constant flow (six asthmatics; two control children). For subjects able to perform the OL technique, OL and VC NO measurements were linearly related (r2 = 0.88). In children, VC NO assays are reproducible, sensitive in identifying asthma, and portable. Additionally, we have shown that (1) not all children are able to perform OL measurements, and (2) VC measurements vary linearly with OL measurements. These findings suggest that there may not be compelling reason to favor OL over VC measurements for hypernitrosopnea in children with asthma.
Doctors should boycott working in Australia's immigration centres and must continue to speak out on mistreatment of detainees--despite the law
Authors: D. Isaacs
Journal: BMJ (2015)

David Isaacs has been to Nauru and seen the suffering among detainees in Australia’s off-shore immigration centre

In 1992 Paul Keating’s Labor government of Australia introduced a controversial policy of mandatory detention of asylum seekers to help cope with rising numbers of Vietnamese, Chinese, and Cambodian refugees. In 2001 John Howard’s Liberal government introduced the “Pacific solution,” which involved excising some islands from the mainland so that they no longer constituted Australian soil and transferred some asylum seekers, who had arrived by boat, to detention centres on the tiny Pacific island of Nauru and later also on Manus Island in Papua New Guinea.1 Some asylum seekers have been sent to detention centres on the mainland. The average time spent in detention before applications for refugee status are processed has lengthened progressively and is now well over a year.2

People seeking asylum in Australia are not told when their applications will be processed, so detention is indefinite—a truly Kafkaesque situation. Strong evidence shows that the harsh conditions under which children and adults are held, particularly on Nauru and Manus, as well as uncertainty about their fate, are highly detrimental to mental health.3 4

The Australian Human Rights Commission’s inquiry examined the …
Decreased Fidelity in Replicating CpG Methylation Patterns in Cancer Cells
Authors: Toshikazu Ushijima, Naoko Watanabe, Kimiko Shimizu, Kazuaki Miyamoto, Takashi Sugimura, Atsushi Kaneda
Journal: Cancer Research (2005)

Abstract The unmethylated or methylated status of individual CpG sites is faithfully copied into daughter cells. Here, we analyzed the fidelity in replicating their methylation statuses in cancer cells. A single cell was clonally expanded, and methylation statuses of individual CpG sites were determined for an average of 12.5 DNA molecules obtained from the expanded population. By counting the deviation from the original methylation patterns inferred, the number of errors was measured. The analysis was done in four gastric cancer cell lines for five CpG islands (CGI), and repeated six times (total 1,495 clones sequenced). HSC39 and HSC57 showed error rates &amp;lt;1.0 × 10−3 errors per site per generation (99.90-100% fidelity) for all the five CGIs. In contrast, AGS showed significantly elevated error rates, mainly due to increased de novo methylation, in three CGIs (1.6- to 3.2-fold), and KATOIII showed a significantly elevated error rate in one CGI (2.2-fold). By selective amplification of fully methylated DNA molecules by methylation-specific PCR, those were stochastically detected in KATOIII and AGS but never in HSC39 and HSC57. When methylation of entire CGIs was examined for eight additional CGIs, KATOIII and AGS had frequent methylation, whereas HSC39 and HSC57 had few. KATOIII and AGS had four and eight times, respectively, as high expression levels of DNMT3B as HSC39. These data showed that some cancer cells have decreased fidelity in replicating methylation patterns in some CGIs, and that the decrease could lead to methylation of the entire CGIs.
The diagnostic yield of the pneumococcal urinary antigen test in clinical practice and its impact on antibiotic therapy
Authors: Wendy Laijen, Dominic Snijders, Wim Boersma
Journal: European Respiratory Journal (2011)

Background:  The pneumococcal urinary antigen test (PUAT) is commonly used for the aetiological diagnose of community-acquired pneumonia (CAP) and can be useful for pathogen-directed therapy. The aim of this study was to evaluate the diagnostic yield of the PUAT and the impact on antibiotic therapy in patients with CAP and a positive PUAT result.   Methods:  A retrospective study of adults hospitalised with CAP between 2005 and 2007 was performed. All patients were tested by PUAT. Sensitivity of the PUAT was determined and whether antibiotic treatment was adapted to the PUAt results.   Results:  681 patients with CAP were included. Causative micro-organisms were isolated by using conventional methods in 243 (35.7%) patients. The pathogen most frequently identified was  S. pneumoniae  in 91 (13.4%) patients, with an increase of diagnostic yield by the PUAT to a total of 178 (26.1%) patients. The PUAT increased the total number of aetiological diagnosis from 35.7% to 48.5%. The PUAT was positive in 37 of 55 patients with definitive pneumococcal pneumonia (67.3%). PUAT was positive in 56 of 95 pneumococcal cases (definite and probable) giving an overall test sensitivity of 59.0%. The test specificity was 93.2%. A positive PUAT led to narrowing antibiotic treatment in 63 (41.2%) patients.   Conclusion:  The PUAT is a useful technique for early detection of  S. pneumoniae  in patients with CAP, but the test is less sensitive in this clinical setting than prospective studies indicate. The PUAT results led the physician to narrow the antibiotic treatment, but insufficient adherence to treatment guidelines of CAP when a PUAT is positive limits its impact.
Malaria medicines: a glass half full?
Authors: Timothy N. C. Wells, Rob Hooft van Huijsduijnen, Wesley C. Van Voorhis
Journal: Nature Reviews Drug Discovery (2015)

Despite considerable advances in malaria medicines in the past 20 years, the global burden of malaria remains substantial. Moreover, continued emergence of drug resistance ensures that new antimalarials will be needed in the near future. Wells and colleagues summarize the current landscape of antimalarial therapies and investigational drugs, highlighting the progress made, identifying gaps in terms of target profiles and recommending priorities for future research. Despite substantial scientific progress over the past two decades, malaria remains a worldwide burden that causes hundreds of thousands of deaths every year. New, affordable and safe drugs are required to overcome increasing resistance against artemisinin-based treatments, treat vulnerable populations, interrupt the parasite life cycle by blocking transmission to the vectors, prevent infection and target malaria species that transiently remain dormant in the liver. In this Review, we discuss how the antimalarial drug discovery pipeline has changed over the past 10 years, grouped by the various target compound or product profiles, to assess progress and gaps, and to recommend priorities.
BRUCELLA ENDOCARDITIS OF CONGENITAL BICUSPID AORTIC VALVE
Authors: Harry F. Wechsler, Einar G. Gustafson
Journal: Annals of Internal Medicine (1942)

Case Reports1 June 1942BRUCELLA ENDOCARDITIS OF CONGENITAL BICUSPID AORTIC VALVEHARRY F. WECHSLER, M.D., EINAR G. GUSTAFSON, M.D.HARRY F. WECHSLER, M.D., EINAR G. GUSTAFSON, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-16-6-1228 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA review of cases of brucellosis with endocarditis recently was reported by Smith and Curtis.1 This entity, despite the prevalence of undulant fever in this country, seems still to be a rarity. Of the 10 cases reported, only five1, 3 have occurred in the United States. The present case is reported because of its rarity and also because it is the first recorded to have been superimposed on a congenital valvular lesion. In addition the pathological changes in the other viscera are of interest.CASE REPORTC. W., aged 28, white male, was admitted to the Lenox Hill Hospital on...References1. SMITHCURTIS KMAC: Brucellosis endocarditis, Am. Jr. Med. Sci., 1939, cxcviii, 342. CrossrefGoogle Scholar2. DE LA CHAPELLE CE: Vegetative endocarditis due to the Brucellus melitensis with a case report, Am. Heart Jr., 1927, iv, 732. Google Scholar3. SPINKNELSON WWAA: Brucellosis endocarditis, ANN. INT. MED., 1939, xiii, 729. Google Scholar4. HUDDLESON IF: Brucella infections in animals and man, 1934, Commonwealth Fund, New York City. Google Scholar5. PARKERDRY RLTJ: Coarctation of aorta at unusual site, associated with congenitally bicuspid aortic valve, Am. Heart Jr., 1938, xv, 739. CrossrefGoogle Scholar6. WECHSLERGUSTAFSON HFE: Coarctation of the aorta (adult type); congenital bicuspid aortic valve; subacute bacterial endocarditis, Am. Heart Jr., 1937, xiv, 107. CrossrefGoogle Scholar7. BROTCHNER RJ: Etiology of hypertension resulting from coarctation of the aorta, Arch. Path., 1939, xxviii, 676. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication November 12, 1940.From the Medical Service of Dr. Otto M. Schwerdtfeger, Lenox Hill Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCardiovascular LocalisationsOcular ManifestationsCardiovascular complicationsSkin manifestationsOcular manifestationsBrucella NephritisGEORGE DUNEA, M.B., M.R.C.P., ROBERT M. KARK, F.R.C.P., F.A.C.P., ROBERT LANNIGAN, M.D., DONALD D'ALESSIO, M.D., ROBERT C. MUEHRCKE, M.D., F.A.C.P.Erkrankungen des EndokardBrucella abortus EndocarditisSubacute bacterial endocarditis of nonstreptococcic etiologyA case of infection with brucella sius, causing endocarditis and nephritis; Death from rupture of mycotic aneurysmPathogenesis of subacute bacterial endocarditis 1 June 1942Volume 16, Issue 6Page: 1228-1233KeywordsAortic valveBrucellaBrucellosisEndocarditisFeversLesionsMedical services ePublished: 1 December 2008 Issue Published: 1 June 1942 PDF downloadLoading ...
Abstract 3555: Utilization of a New Echocardiographic Screening Tool for the Assessment of Aortic Stenosis in the Setting of Left Ventricular Systolic Dysfunction
Authors: William H Hansen, Thomas R Behrenbeck, Gregory Gilman, Maurice E Sarano, James B Seward
Journal: Circulation (2006)

Evaluating aortic stenosis (AS) in patients with low left ventricular ejection fraction (LV EF) can pose a diagnostic challenge. Previously, we introduced a new parameter for the assessment of aort...
Smoking cessation in tuberculosis and COPD patients
Authors: N.V. Yahorava, H.L. Hurevich, A.A. Rimga, A.M. Skrahina, T.M. Krytskaya
Journal: European Respiratory Journal (2011)

The aim of this study was to investigate clinical, nicotine dependence status in smoking tuberculosis (TB) and COPD pts, efficacy of treatment of nicotine dependence by nicotinic acetylcholine receptor agonist (cytizine), mexidol, behavioural intervention in TB and COPD pts.   Methods:  91 smoking TB and COPD pts (74m, 17w, age 41±1) were examined before and after 3 months of treatment. 50 Pts have been treated with 4-5 antituberculosis drugs, basic course of COPD (β2-agonist, anticholinergic, corticoids, O2), cytizine (1,5-6mg/day-25days), mexidol (100mg/day-25days), behavioural intervention. 41 Pts have received 4-5 antituberculosis drugs and basic course of COPD only (Gr2). Examination of clinical status, blood gases, pulmonary function tests, quiz pts about their smoking status had been performed in all pts.   Results:  In TB and COPD pts was found low nicotine dependence, low motivation to quit. After 3 months of treatment in TB and COPD pts clinical status was improved. Smoking cessation was achieved in 16% pts of Gr1, decrease of nicotine consumption-in 60% pts of Gr1. In 76% pts of Gr1, in 71% pts of Gr2 was found improvement of chest X-ray. Sputum conversion was found in 80% pts of Gr1, in 73% pts of Gr2. In Gr1 was found increase of forced expiratory volume in 1 second for predicted on 14%, p   Conclusion:  In TB and COPD pts adding cytizine, mexidol, behavioural intervention to antituberculosis and basic course of COPD leads to decrease of level of nicotine consumption, improvement of clinical, blood gases exchange status, pulmonary function.
STUDIES OF CALCIUM AND PHOSPHORUS METABOLISM
Authors: Fuller Albright, Walter Bauer, Marion Ropes, Joseph C. Aub
Journal: Journal of Clinical Investigation (1929)

In the course of our studies in calciulm metabolism evidence has steadily accumulated that the metabolism of acid-producing substances plays an important r6le in influencing the assimilation and excretion of calcium. This effect, however, has not been adequately studied in man, and in other studies of calcium exchange the potential acidity or alkalinity of foods and medication has largely been neglected. It is the purpose of the present investigation to follow the effect of food-stuffs and inorganic salts on calcium metabolism with relation to their potential acidity (after oxidation) referred to the hydrogen ion concentration of the blood. Studies in rickets for some time have indicated the importance of acidity to the assimilation and storage of inorganic salts in bone. Thus, McClendon (1) noted that the addition of alkali to a diet increased its power to produce rickets and, conversely, Zucker, Johnson, and Barnett (2) reported that the change in acidity of diets from the alkaline toward the acid side of neutrality might result in healing of the rachitic lesions. Much work, too, has been done upon the effect of administered acid on the mineral excretion. The experiments of Givens and Mendel (3) and of Givens (4) upon the effect of base and acid on the general metabolism tended to minimize variations in calcium excretion resulting from this factor. Subsequently, Goto (5), using rabbits, demonstrated depletion of the skeleton by repeated doses of hydrochloric acid. Lamb and Evvard (6) demonstrated increased urinary calcium
Abstract P139: Do Your Income and Occupation Affect Your Leisure Time Physical Activity? Evidence from NHANES 1999-2006
Authors: Lisa Kakinami, Tracie Barnett, Lise Gauvin, Gilles Paradis
Journal: Circulation (2013)

Background: Over ¾ of Americans fail to meet the AHA recommendations for leisure time physical activity (LTPA), with higher proportions found among lower income adults. However, this association may be moderated by activity levels that are necessary as a part of daily life, such as active transportation among those that cannot afford a vehicle, or physical labor in some lower wage-earning occupations. Data are limited to studies either not distinguishing between occupational and daily life PA, or using broad occupation job titles which may not represent the PA on an individual level. Objective: Determine the association between activity levels of daily life and LTPA. Methods: Participants were adults (20+ years) from the 1999-2006 National Health and Nutrition Examination Survey. Analyses were stratified by self-reported lifestyle (work, housework and school): 1) sedentary during the day (n=4233); 2) minimally active: stands or walks but does not carry or lift things often (n=11,853); 3) moderately active: carries light objects, or climbs hills often (n=4117); and 4) and very active: carries heavy objects (n=1586). Multivariable linear regression analyzed the association between annual household income (&lt;$20K, $20K-45K, $45K-75K, $75K+ [reference]) and self-reported weekly minutes of moderate, vigorous, and total LTPA. Analyses included sampling weights to account for NHANES’ complex sampling design and adjusted for sex, age, marital status, ethnicity, weight status, whether the person actively commuted, and number of hours worked per week. Results: Lower income participants that were either very active, or sedentary during the day reported significantly less LTPA than those with comparable daily life activity levels but annual income $75K+. Conclusions: A gradient relationship between income and LTPA was seen in the two lifestyle extremes: the sedentary and very active. Public health actions aimed at increasing LTPA should be multimodal and aimed at changing both messaging and environments likely to promote LTPA.
Omalizumab add-on therapy reduces exacerbations among responders: A pooled NNT analysis from 5 phase 3 studies
Authors: Ismail Kasujee, Giovanni Bader
Journal: European Respiratory Journal (2014)

Introduction   Omalizumab, an anti-IgE monoclonal antibody is recommended for long-term treatment of patients with moderate-to-severe allergic asthma that are identified by the physician9s global evaluation of treatment effectiveness (GETE) tool after 16 weeks of therapy. This post-hoc pooled analysis investigated the effect of omalizumab vs. placebo (PBO) on exacerbations in GETE responders (patients with good/excellent rating).   Methods   Data from 5 randomised, double-blind, placebo-controlled phase 3 studies were pooled and annualised clinically significant exacerbation (any worsening of asthma considered by the treating physician to require systemic corticosteroids) rates were analysed in GETE responders and non-responders to omalizumab and PBO therapy. The number needed-to-treat (NNT) to save one exacerbation in 1 year was calculated.   Results   Omalizumab significantly reduced the annualised clinically significant exacerbation rate in responders (n=553) by 63% vs. the overall PBO group (n=801) and by 51% vs. the PBO responders (n=306; Figure). The NNT to save one clinically significant exacerbation in 1 year for omalizumab was 1.19 vs. the overall PBO group and 1.96 vs. PBO responders.   Conclusions   Omalizumab responders, as identified by GETE, are associated with significantly lower exacerbations rates compared with those on placebo. GETE is a tool that can help identify those who benefit from omalizumab therapy.