108 research outputs found

    Clinical predictors of fulminant colitis in patients with Clostridium difficile infection

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    Background/Aim: Clostridium difficile infection (CDI) can affect up to 8% of hospitalized patients. Twenty-five percent CDI patients may develop C. difficile associated diarrhea (CDAD) and 1-3% may progress to fulminant C. difficile colitis (FCDC). Once developed, FCDC has higher rates of complications and mortality. Patients and Methods: A 10-year retrospective review of FCDC patients who underwent colectomy was performed and compared with randomly selected age- and sex-matched non-fulminant CDAD patients at our institution. FCDC (n=18) and CDAD (n=49) groups were defined clinically, radiologically, and pathologically. Univariate analysis was performed using Chi-square and Student′s t test followed by multivariate logistic regression to compute independent predictors. Results: FCDC patients were significantly older (77 ± 13 years), presented with triad of abdominal pain (89%), diarrhea (72%), and distention (39%); 28% had prior CDI and had greater hemodynamic instability. In contrast, CDAD patients were comparatively younger (65 ± 20 years), presented with only 1 or 2 of these 3 symptoms and only 5% had prior CDI. No significant difference was noted between the 2 groups in terms of comorbid conditions, use of antibiotics, or proton pump inhibitor. Leukocytosis was significantly higher in FCDC patients (18.6 ± 15.8/mm 3 vs 10.7 ± 5.2/mm 3 ; P=0.04) and further increased until the point of surgery. Use of antiperistaltic medications was higher in FCDC than CDAD group (56% vs 22%; P=0.01). Conclusions: Our data suggest several clinical and laboratory features in CDI patients, which may be indicative of FCDC. These include old age (>70 years), prior CDI, clinical triad of increasing abdominal pain, distention and diarrhea, profound leukocytosis (>18,000/mm 3 ), hemodynamic instability, and use of antiperistaltic medications

    Heterotrimeric kinesin-II is necessary and sufficient to promote different stepwise assembly of morphologically distinct bipartite cilia in<i>Drosophila</i>antenna

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    Structurally diverse sensory cilia have evolved from primary cilia, a microtubule-based cellular extension engaged in chemical and mechanical sensing and signal integration. The diversity is often associated with functional specialization. The olfactory receptor neurons in Drosophila, for example, express three distinct bipartite cilia displaying different sets of olfactory receptors on them. Molecular description underlying their assembly and diversification is still incomplete. Here, we show that the branched and the slender olfactory cilia develop in two distinct step-wise patterns through the pupal stages before the expression of olfactory receptor genes in olfactory neurons. The process initiates with a thin procilium growth from the dendrite apex, followed by volume increment in successive stages. Mutations in the kinesin-II subunit genes either eliminate or restrict the cilia growth as well as tubulin entry into the developing cilia. Together with previous results, our results here suggest that heterotrimeric kinesin-II is the primary motor engaged in all type-I sensory cilia assembly in Drosophila and that the cilia structure diversity is achieved through additional transports supported by the motor during development.</jats:p

    Synthetic Studies With Pinus Elliottiis' Rosin Derivatives. Oxidation Of Maleopimaric Anhydride Methyl Ester And Trimethyl Fumaropimarate

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    Ozonolysis of maleopimaric anhydride methyl ester in the presence of tetracyanoethylene led to an epoxide and an ozonide. Ozonolysis of the trimethyl fumaropimarate, followed by treatment with Me2S, led to an epoxide, a diene, a keto-acid and an allylic oxidation product. Some of the compounds obtained were active against Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus.1115963Seebacher, W., Hüfner, A., Haslingeer, E., Weis, R., (1995) Monatsh. Chem., 129, p. 697. , and references cited thereinKsabati, M.B., Schimtz, F.J., (1987) J. Org. Chem., 52, p. 3766Miyamoto, T., Sakamoto, K., Arao, K., Komori, T., Higuchi, R., Sasaki, T., (1996) Tetrahedron, 52, p. 8187Zalkow, L.H., Ford, R.A., Kutney, J.P., (1962) J. Org. Chem., 27, p. 3535Zalkow, L.H., Brannon, D.R., (1964) J. Org. Chem., 29, p. 1296Zalkow, L.H., Girotra, N.N., (1963) J. Org. Chem., 28, p. 2033Zalkow, L.H., Kulkarni, M.V., Girotra, N.N., (1965) J. Org. Chem., 30, p. 1679Halbrook, N.J., Lawrence, R.V., Dressler, R.L., Blackstone, R.C., Herz, W., (1964) J. Org. Chem., 29, p. 1017Santos, C., Rosso, C.R.S., Imamura, P., (1999) M. Synth. Commun., 29, p. 1903Bailey, P.S., (1978) Ozonization in Organic Chemistry, 1. , Academic Press, New YorkHerz, W., Blackstone, R.C., (1969) Atmos Environ, 34, p. 1257Atmos Environ, p. 135Masaki, Y., Miura, T., Ochiai, M., (1996) Bull. Chem. Soc. Jpn., 69, p. 195. , and references cited thereinThe ozonide could be stored in a freezer without decomposition at -5°C for few weeksShiojima, K., Masuda, K., Ageta, K., (1990) Chem. Pharm. Bull., 38, p. 79Li, T., Yang, Y., Li, Y., (1993) J. Chem. Res. (S), p. 30Carlsen, P.H.J., Katsuki, T., Martin, V.S., Sharpless, K.B., (1981) J. Org. Chem., 46, p. 3936Funk, R.L., Abelman, M.M., (1986) J. Org. Chem., 51, p. 3247For convenience, the numbering of carbons for 14 was used the same given for 3Sam, D.J., Simmons, H.F., (1972) J. Am. Chem. Soc., 94, p. 4024Ferreira, J.T.B., Cruz, W.O., Vieira, P.C., Yonashiro, M., (1987) J. Org. Chem., 52, p. 3698Mitra, R.B., Muljiani, Z., Deshmukh, A.R.A., (1982) S. Synth. Commun., 12, p. 1063Aristoff, P.A., Johnson, P.D., Harrison, A.W., (1985) J. Am. Chem. Soc., 107, p. 7961Homans, A.L., Fuchs, A., (1970) J. Chromatogr., 75, p. 327Hamburger, M.O., Cordell, G.A., (1987) J. Nat. Prod., 50, p. 19Bruch, M.K., (1991) Methods of Testing Antiseptics: Antimicrobials Used Topically in Humans and Procedures for Hand Scrubs, in Disinfection, Sterilization and Preservation, 4th. Ed., , Lea & Febinger, PhiladelphiaHalbrook, N.J., Lawrence, R.V., (1958) J. Am. Chem. Soc., 80, p. 36

    The Relationship Between Obesity and Atherosclerotic Progression and Prognosis Among Patients With Coronary Artery Bypass Grafts The Effect of Aggressive Statin Therapy

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    ObjectivesThis study examines whether obesity accelerates atherogenic progression or adverse outcomes after coronary artery bypass graft (CABG) surgery.BackgroundObesity is a major risk factor for developing coronary heart disease. Whether obesity accelerates disease progression after CABG is unclear.MethodsWe examined how body mass index (BMI) related to atherosclerotic graft progression and a clinical composite outcome of death, nonfatal myocardial infarction, stroke, CABG surgery, or angioplasty among 1,314 participants in the Post CABG trial. Participants who had undergone CABG surgery were randomly assigned in a 2 × 2 factorial design to warfarin versus placebo and aggressive low-density lipoprotein cholesterol (LDL-C) lowering with lovastatin 40 to 80 mg/day (to achieve LDL-C of 60 to 85 mg/dl) versus moderate LDL-C lowering with lovastatin 2.5 to 5 mg/day (to achieve LDL-C of 130 to 140 mg/dl). Angiographic progression was assessed by coronary angiography at 4 to 5 years.ResultsHigher BMI was associated with a higher likelihood of angiographic progression (p trend = 0.003) after adjustment for demographic factors, treatment assignment, smoking status, and years since CABG surgery, but not with clinical events (p trend = 0.81). In stratified analyses, higher BMI was associated with angiographic progression in the low-dose lovastatin group (p trend <0.001) but not in the high-dose group (p = 0.03 for test for interaction of BMI and statin treatment). In the high-dose lovastatin group, higher BMI appeared to be protective against clinical events (p trend = 0.06, test of interaction: 0.02).ConclusionsHigher BMI is strongly associated with atherogenic progression after CABG surgery. Aggressive statin therapy may be protective against obesity-related acceleration of coronary heart disease

    Orco associates with the C-terminal ’tail’ domain of the kinesin-2 motor subunits.

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    (A) Schematic illustrates the organisation of Drosophila kinesin-2 and the tail domains of the motor subunits. (B) Co-immunoprecipitation of the Drosophila kinesin-2 subunits from the head extracts of flies expressing GFP:Orco (driven by chaGal4) using agarose beads conjugated with GFP-nanobody. (C, D) Affinity copurification of GFP:Orco (C), and OR47b (D), respectively, from the adult head extracts by using the GST tagged kinesin2 tail fragments, KLP64D-T and KLP68D-T.</p

    Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis

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    Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer

    Double outlet of both ventricles: morphological, echocardiographic and surgical considerations

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    \ua9 The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. OBJECTIVES: To describe the morphology, echocardiographic features and surgical management of the entity appropriately described as \u27double outlet of both ventricles\u27. METHODS: Seven patients (5 males, age 0.5-7.5 months) were diagnosed to have a unique form of subarterial ventricular septal defect (VSD) and ventriculo-arterial connection, where a muscular outlet septum straddled the crest of the ventricular septum in a cruciate manner, such that both great arteries were equally committed to both ventricles. Diagnosis was established by echocardiography, with 6 patients submitted to surgical repair by means of intracardiac routing of the left ventricle to the aorta using 2 patches. RESULTS: Surgical repair was successful in all 6 patients in whom it was attempted. In addition, 1 patient underwent concomitant repair of aortic coarctation, and 2 had closure of multiple VSDs. We lost 1 patient to follow-up after diagnosis. Follow-up with a range from 3 months to 8 years in the remaining patients revealed all to be clinically well with satisfactory growth of both outflow tracts. CONCLUSIONS: We describe a series of patients with the ventriculo-arterial connection best described as \u27double outlet of both ventricles\u27. Diagnosis is readily established by echocardiography. Good early and midterm results can be expected subsequent to surgical repair using 2 patches for interventricular septation

    Valuation of innovation: The case of iPhone

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    We estimate the private value of Apple’s iPhone by observing abnormal stock market reactions to news announcements and patent publications related to the innovation. Our estimate of the lower bound on the market valuation of iPhone is fairly high, at minimum 30 billion U.S. (event day) dollars. We find that patentable technology explains about 25% of that total value. We also find a weak negative reaction among Apple’s rivals to the news about iPhone but no significant reaction to the publication of patent documents concerning iPhone can be observed. The evidence suggests that the value of iPhone primarily stems from Apple’s management and marketing abilities and efforts rather than from underlying "hard" technologies and intellectual property.innovation, R&D, patent, iPhone, valuation
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