tbuckley/cabot-search huggingface dataset:
Monetary Costs of Dementia in the United States
Authors: Michael D. Hurd, Paco Martorell, Adeline Delavande, Kathleen J. Mullen, Kenneth M. Langa
Journal: New England Journal of Medicine (2013)

Dementia affects a large and growing number of older adults in the United States. The monetary costs attributable to dementia are likely to be similarly large and to continue to increase.
THE CARRIER PROBLEM AT HOME IN TIME OF WAR
Authors: E. C. Hort
Journal: BMJ (1915)

stick together, and slhould be opened gently.After the bags have been used, the otutside shoulid be washed, dried withi a duster and in tlhe air, and powdered witlh Frencl clhalk.They shiould then be turned inside out and washed again, after wlichl they' shouldl be dried with a cloth and in the air.The outer surface of caclh bag slhould then be painted with t tlhin layer of the pre- paration provided for the purpose.Bags hung in a well-ventilated place slhouild be ready for use again in about twelve hours.In a well-ventilated, dry, .armplace the drying may be completed in four hours.The bags should be then thorouglhly powdered with French chalk both inside and out.By this process the waterproofness of tlle bags-wlicih is redtuced by wear, specially after marclles-is 'restored.
Enhanced Exon-skipping Induced by U7 snRNA Carrying a Splicing Silencer Sequence: Promising Tool for DMD Therapy
Authors: Aurélie Goyenvalle, Arran Babbs, Gert-Jan B van Ommen, Luis Garcia, Kay E Davies
Journal: Molecular Therapy (2009)

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. In most cases, the open-reading frame is disrupted which results in the absence of functional protein. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD and has recently been shown to correct the reading frame and restore dystrophin expression in vitro and in vivo. Specific exon skipping can be achieved using synthetic oligonucleotides or viral vectors encoding modified small nuclear RNAs (snRNAs), by masking important splicing sites. In this study, we demonstrate that enhanced exon skipping can be induced by a U7 snRNA carrying binding sites for the heterogeneous ribonucleoprotein A1 (hnRNPA1). In DMD patient cells, bifunctional U7 snRNAs harboring silencer motifs induce complete skipping of exon 51, and thus restore dystrophin expression to near wild-type levels. Furthermore, we show the efficacy of these constructs in vivo in transgenic mice carrying the entire human DMD locus after intramuscular injection of adeno-associated virus (AAV) vectors encoding the bifunctional U7 snRNA. These new constructs are very promising for the optimization of therapeutic exon skipping for DMD, but also offer powerful and versatile tools to modulate pre-mRNA splicing in a wide range of applications. Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. In most cases, the open-reading frame is disrupted which results in the absence of functional protein. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD and has recently been shown to correct the reading frame and restore dystrophin expression in vitro and in vivo. Specific exon skipping can be achieved using synthetic oligonucleotides or viral vectors encoding modified small nuclear RNAs (snRNAs), by masking important splicing sites. In this study, we demonstrate that enhanced exon skipping can be induced by a U7 snRNA carrying binding sites for the heterogeneous ribonucleoprotein A1 (hnRNPA1). In DMD patient cells, bifunctional U7 snRNAs harboring silencer motifs induce complete skipping of exon 51, and thus restore dystrophin expression to near wild-type levels. Furthermore, we show the efficacy of these constructs in vivo in transgenic mice carrying the entire human DMD locus after intramuscular injection of adeno-associated virus (AAV) vectors encoding the bifunctional U7 snRNA. These new constructs are very promising for the optimization of therapeutic exon skipping for DMD, but also offer powerful and versatile tools to modulate pre-mRNA splicing in a wide range of applications.
The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy
Authors: L D Wang, T N Rao, R G Rowe, P T Nguyen, J L Sullivan, D S Pearson, S Doulatov, L Wu, R C Lindsley, H Zhu, D J DeAngelo, G Q Daley, A J Wagers
Journal: Leukemia (2015)
Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies
Authors: Sabine Kayser, Manuela Zucknick, Konstanze Döhner, Jürgen Krauter, Claus-Henning Köhne, Heinz A. Horst, Gerhard Held, Marie von Lilienfeld-Toal, Sibylla Wilhelm, Mathias Rummel, Ulrich Germing, Katharina Götze, David Nachbaur, Brigitte Schlegelberger, Gudrun Göhring, Daniela Späth, Carina Morlok, Veronica Teleanu, Arnold Ganser, Hartmut Döhner, Richard F. Schlenk
Journal: Blood (2011)
Effect of tobacco smoke exposure on rat tracheal submucosal glands: an ultrastructural study.
Authors: D J Lewis, P R Jakins
Journal: Thorax (1981)

The ultrastructural appearance of rat tracheal submucosal glands after exposure to tobacco smoke for up to two years is described. Within the mucous cells many of the rough endoplasmic reticulum cisternae were grossly dilated with an accumulation of amorphous, electron-lucent material. The Golgi zones were prominent, and the secretion granules often contained dense cores, and appeared to have coalesced. Histochemically, increased amounts of sulphated mucus were present in exposed rats. Serous, ciliated, and myoepithelial cells were unaffected by smoke exposure.
BIOLOGICAL STUDIES OF THE TUBERCLE BACILLUS
Authors: W. Steenken, W. H. Oatway, S. A. Petroff
Journal: The Journal of Experimental Medicine (1934)

1. The H(37) strain of human tubercle bacillus has been dissociated into two variants,-the R, or avirulent, and the S, or virulent, variants. 2. When their dissociation is complete, colony morphology for each is distinctive and typical. 3. The morphology of the individual bacilli of the two variants is different and characteristic. 4. The R variant develops best in an acid medium; the S develops best in an alkaline medium. 5. A method of assortment to facilitate the procedure of forced dissociation has been described. 6. The difference in virulence has been proven by observations on the pathogenesis of the variants.
Genome-wide association analyses provide genetic and biochemical insights into natural variation in rice metabolism
Authors: Wei Chen, Yanqiang Gao, Weibo Xie, Liang Gong, Kai Lu, Wensheng Wang, Yang Li, Xianqing Liu, Hongyan Zhang, Huaxia Dong, Wan Zhang, Lejing Zhang, Sibin Yu, Gongwei Wang, Xingming Lian, Jie Luo
Journal: Nature Genetics (2014)
Recognition and initial management of ovarian cancer: summary of NICE guidance
Authors: C. Redman, S. Duffy, N. Bromham, K. Francis
Journal: BMJ (2011)

Ovarian cancer is the leading cause of death from gynaecological cancer in the United Kingdom, and its incidence is rising. It is the fifth most common cancer in women, with a lifetime risk of about 2% in England and Wales.1 The outcome for women with ovarian cancer is generally poor, with an overall five year survival rate of less than 35%.2 Most women have had symptoms for months before presentation, and as these are frequently non-specific, delays often occur between presentation and referral to a specialist.3 Greater awareness of the disease and appropriate initial investigations in primary and secondary care are needed to enable earlier referral and optimum treatment. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the recognition and initial management of women with ovarian cancer.4 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Detection in primary care #### Awareness of symptoms and signs
Rita Walford (nee Gleiberman)
Authors: D. Walford
Journal: BMJ (2010)

Rita Walford was born in Birmingham on 7 June 1915, the fourth of six children. Her eldest sister was struck down with meningitis at the age of 2 and that remained her mental age until her death at the age of 20, while a younger brother was born with bilateral talipes equinus. The corrective treatment required was beyond the family’s means, but their wonderful pre-NHS general practitioner persuaded the orthopaedic surgeon to waive his fees and the treatment was successful. From these early experiences came Rita’s burning ambition to study medicine, although the odds were very much stacked against her.

Awarded a foundation scholarship in 1927 to King Edward VI High …
How Contagious Are Common Respiratory Tract Infections?
Authors: Joshua D. Hartzell, Charles N. Oster, Joel C. Gaydos
Journal: New England Journal of Medicine (2003)

To the Editor: Musher (March 27 issue)1 points out that adenoviruses have caused large outbreaks among military recruits, but additional comment is needed. Adenoviruses do cause epidemics in young adults.2–5 Before vaccination, adenovirus-associated acute respiratory disease affected up to 10 percent of recruits and was responsible for nearly 70 percent of respiratory disease.3 Implementation of an adenovirus-vaccination policy in the military in 1971 resulted in a dramatic reduction in the occurrence of adenovirus-associated acute respiratory disease, but the manufacturer stopped producing the vaccines in 1995.3 Since then, a substantial number of outbreaks of adenovirus infection have occurred.3–5 Administration . . .
Natural T-cell responses against minor histocompatibility antigen (mHag) HY following HLA-matched hematopoietic cell transplantation: what are the requirements for a ‘good’ mHag?
Authors: T Kollgaard, S Reker Hadrup, S L Petersen, T N Masmas, M H Andersen, E Spierings, L Vindeløv, P thor Straten
Journal: Leukemia (2008)
Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: cohort study based on prospective data
Authors: M. Klein, I. Gogenur, J. Rosenberg
Journal: BMJ (2012)

<b>Objectives</b> To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection. <b>Design</b> Cohort study based on data from a prospective clinical database and electronically registered medical records. <b>Setting</b> Six major colorectal centres in eastern Denmark. <b>Participants</b> 2766 patients (1441 (52%) men) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009. Median age was 70 years (interquartile range 62-77). <b>Intervention</b> Postoperative use of NSAID (defined as at least two days of NSAID treatment in the first seven days after surgery). <b>Main outcome measures</b> Frequency of clinical anastomotic leakage verified at reoperation; mortality at 30 days. <b>Results</b> Of 2756 patients with available data and included in the final analysis, 1871 (68%) did not receive postoperative NSAID treatment (controls) and 885 (32%) did. In the NSAID group, 655 (74%) patients received ibuprofen and 226 (26%) received diclofenac. Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment, compared with controls (12.8% and 8.2% <i>v</i> 5.1%; P&lt;0.001). After unadjusted analyses and when compared with controls, more patients had anastomotic leakage after treatment with diclofenac (7.8% (95% confidence interval 3.9% to 12.8%)) and ibuprofen (3.2% (1.0% to 5.7%)). But after multivariate logistic regression analysis, only diclofenac treatment was a risk factor for leakage (odds ratio 7.2 (95% confidence interval 3.8 to 13.4), P&lt;0.001; ibuprofen 1.5 (0.8 to 2.9), P=0.18). Other risk factors for anastomotic leakage were male sex, rectal (<i>v</i> colonic) anastomosis, and blood transfusion. 30 day mortality was comparable in the three groups (diclofenac 1.8% <i>v</i> ibuprofen 4.1% <i>v</i> controls 3.2%; P=0.20). <b>Conclusions</b> Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery. Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis. Large scale, randomised controlled trials are urgently needed.
Bronchoscopic Photography of a Bronchial Carcinoid Tumor Associated with Unilateral Hypoperfusion of the Lung
Authors: S.K. Pingleton
Journal: Endoscopy (1983)

A patient with a bronchial carcinoid-producing unilateral hypoperfusion of the lung is described. Bronchoscopic photographs show the adenoma to assume different intrabronchial positions during inspiration and expiration. Although patent during inspiration, the lumen was effectively occluded during expiration. The adenoma exhibited a ball-valve movement which is speculated to be the initial mechanism of hypoperfusion in this setting.
Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension
Authors: Charlotte Wagner, Alexander Jobs, Frank Schweda, Lisa Kurtz, Birguel Kurt, Maria L. Sequeira Lopez, R. Ariel Gomez, Toon A.B. van Veen, Cor de Wit, Armin Kurtz
Journal: Kidney International (2010)
Role of chemosensitivity in intrathoracic pressure changes during obstructive sleep apnea.
Authors: E Sforza, A Boudewijns, B Schnedecker, M Zamagni, J Krieger
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We tested the hypothesis that the awake ventilatory response to hypoxia and hypercapnia may contribute to the variability of respiratory effort developed in response to upper airway obstruction in obstructive sleep apnea syndrome. The polygraphic recordings of 38 patients diagnosed as having obstructive sleep apnea on the basis of an apnea+hypopnea index greater than 10 were examined. All subjects received hypoxic and hypercapnic ventilatory tests the day before the nocturnal polysomnography. Thirty apneas during non-rapid eye movement (NREM) sleep and at least 10 apneas during rapid eye movement sleep were analyzed. For each considered apnea, we measured esophageal pressure (Pes) swings during the first three breaths preceding apnea and during the first three and last three occluded efforts occurring during the apnea. We considered as indices of respiratory effort the overall increase from the minimum to the maximum Pes (delta Pes), the rate of increase of Pes during apnea (RPes), and the maximal respiratory effort at the end of apnea (Pes max fin). In NREM sleep, all three indices of respiratory effort were correlated positively with the awake ventilatory response to hypoxia or hypercapnia and with the apnea index. No correlation was found between the indices of respiratory effort and body mass index, age, pulmonary function tests, awake blood gases, apnea duration, and apnea desaturation. In rapid eye movement sleep, none of the considered variables predicted the degree of respiratory effort. In conclusion, our results suggest that the degree of ventilatory response to upper airway occlusion in obstructive sleep apnea may be influenced by the sensitivity of central neural drive to chemical stimuli.
Advancing the War on Malaria
Authors: Jennifer Fisher Wilson
Journal: Annals of Internal Medicine (2003)

Current Clinical Issues15 April 2003Advancing the War on MalariaJennifer Fisher WilsonJennifer Fisher WilsonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-8-200304150-00039 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Malaria is a microcosm of all the problems that exist in global health care, and combating it is no small job. It is the most common and deadly parasitic disease, and one of the top three killer diseases along with tuberculosis and HIV/AIDS. Every year, hundreds of millions of malaria infections occur and 3 million people die of the disease.Malaria's weakening effect on a nation's workforce can be devastating, too. In endemic regions, personal income levels languish at a third less than in a similar-sized nation without malaria, and the gross national product can be reduced by up to ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAdvancing the War on Malaria Whitney Addington , Jo Lines , Julia Mortimer , and Jayne Webster Metrics Cited ByCerebral malariaAdvancing the War on MalariaWhitney Addington, MD, Jo Lines, Julia Mortimer, and Jayne Webster 15 April 2003Volume 138, Issue 8Page: 693-696KeywordsAntimalarialsChloroquineDrugsGlobal healthImmunityInfectious diseasesMalariaMefloquineScientistsVaccines ePublished: 15 April 2003 Issue Published: 15 April 2003 CopyrightCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Bacteroides Infections
Authors: William E. Smith, Marian W. Ropes
Journal: New England Journal of Medicine (1945)

THE gram-negative anaerobic bacilli that do not bear spores have been grouped together in a genus to which the name "Bacteroides" has been assigned.1 There are many reports of human infections caused by Bacteroides, but the occurrence of such cases is not widely appreciated. During the last four years, 20 cases have been seen at this hospital (Table 1). On the basis of cases reported in the literature and those seen here, an attempt will be made to describe the clinical aspects of these infections, with the purpose of calling attention to the various conditions in which Bacteroides infection should . . .
Effect of reduced blood flow on alpha 1- and alpha 2-adrenoceptor constriction of rat skeletal muscle microvessels.
Authors: K M McGillivray-Anderson, J E Faber
Journal: Circulation Research (1991)

Adrenergic constriction of skeletal muscle arterioles, particularly small terminal arterioles, is opposed by decreased blood flow or increased metabolic rate. Our previous studies indicate that neural constriction of large arterioles, which have both postjunctional alpha 1- and alpha 2-adrenoceptors, is mediated by alpha 1-receptors; small arterioles depend on alpha 2-receptors. Also, alpha 2, but not alpha 1, constriction is reduced by acidosis. Differential sensitivity of alpha 1 versus alpha 2 constriction to metabolic signals such as H+ may underlie the sensitivity of arteriolar adrenergic constriction to metabolic inhibition. To examine this hypothesis, we studied the effect of reduced perfusion on alpha 1- versus alpha 2-mediated constriction of large arterioles and venules. Intravital microscopy of rat cremaster skeletal muscle was used to obtain concentration-response curves for phenylephrine (alpha 1-agonist) and UK-14,304 (alpha 2-agonist). Thirty percent reduction in cremasteric artery flow by venous outflow obstruction had no effect on baseline diameter, indicating no effect on "intrinsic tone." Reduced perfusion also had no effect on arteriolar or venular sensitivity to phenylephrine or venular sensitivity to UK-14,304 but significantly attenuated arteriolar response to UK-14,304. To examine a possible mechanism for the selective inhibition of alpha 2 constriction by acidosis, we determined the effect of acidosis on the partial alpha 1-agonist St587. Like alpha 2 constriction, St587-mediated constriction of arterioles was reduced during acidosis and was attenuated by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection
Authors: Michael R. Charlton, Alexander Thompson, Bart J. Veldt, Kym Watt, Hans Tillmann, John J. Poterucha, Julie K. Heimbach, David Goldstein, John McHutchison
Journal: Hepatology (2010)

Polymorphism in the interleukin-28B ( IL28B ) gene region, encoding interferon (IFN)-λ3, is strongly predictive of response to antiviral treatment in the nontransplant setting. We sought to determine the prevalence and impact on clinical outcomes of donor and recipient IL28B genotypes among liver transplant recipients. The cohort study included 189 consecutive patients infected with hepatitis C virus (HCV) who underwent liver transplantation between January 1, 1995, and January 1, 2005, at the Mayo Clinic, Rochester, MN. Genotyping of the polymorphism rs12979860 was performed on DNA collected from all donors and recipients in the cohort. Sixty-five patients received IFN-based antiviral therapy. The CC IL28B variant was less common in the chronic HCV-infected recipients than in non-HCV donor livers (33% versus 47%, P = 0.03). IL28B recipient genotype was significantly predictive of fibrosis stage, with TT genotype being associated with more rapid fibrosis (Pearson chi-square P = 0.024 for the comparison G versus A). Donor and recipient IL28B genotype were independently associated with sustained virologic response ( P &lt; 0.005). The presence of IL28B CC variant in either the recipient (R) or donor (D) liver was associated with increased rate of sustained virologic response (D-non-CC/R-non-CC = 3/19 [16%] versus D-CC/R-non-CC = 11/22 [50%] versus D-non-CC/R-CC = 5/12 [42%] versus R-CC/D-CC = 6/7 [86%], P = 0.0095). IL28B genotype was not significantly associated with survival (overall/liver-related). Conclusion: Recipient IL28B TT genotype is associated with more severe histological recurrence of HCV. Recipient and donor liver IL28B genotype are strongly and independently associated with IFN-based treatment response in patients after orthotopic liver transplantation. The data suggest that CC donor livers might be preferentially allocated to patients with HCV infection. (Hepatology 2011;)