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1.
J Clin Gastroenterol ; 2023 Nov 27.
Article En | MEDLINE | ID: mdl-38019086

GOALS: The aim was to assess patient adherence to multitarget stool DNA testing as well as factors associated with adherence. BACKGROUND: In the United States, disparities in colorectal cancer screening exist along racial and socioeconomic lines. While some studies suggest that stool-based screening tests may help reduce the screening gap, the data for multitarget stool DNA testing is unclear. STUDY: We conducted a single-center retrospective cohort study on multitarget stool DNA testing ordered between April 2020 and July 2021. We calculated the proportion of patients who completed testing and used multivariate logistic regression to identify covariates associated with test adherence. RESULTS: Among 797 patients ordered for multitarget stool DNA testing, 481 patients (60.4%) completed testing. Adherence rates by patient subgroups ranged from 35.8% to 78.1%. Higher test adherence was found in Asian patients (odds ratio 2.65, 95% CI 1.36-5.18) and those who previously completed colorectal cancer screening (OR 1.45, 95% CI 1.01-2.09), while Black patients (OR 0.58, 95% CI 0.39-0.87), patients with resident primary care physicians (OR 0.34, 95% CI 0.21-0.56), and patients contacted through an outreach program (OR 0.47, 95% CI 0.25-0.87) had lower adherence. CONCLUSIONS: A significant proportion of patients ordered for multitarget stool DNA testing did not complete testing. Differences in adherence rates among patient subgroups may be reflective of underlying disparities in health care access.

2.
South Med J ; 113(11): 578-584, 2020 11.
Article En | MEDLINE | ID: mdl-33140112

OBJECTIVES: Hepatic encephalopathy (HE) is associated with hospital readmissions and mortality. We sought to determine whether cognitive testing and stool frequency at discharge predicted 30-day readmission or death in cirrhotic patients admitted with overt HE. METHODS: We approached consecutive inpatients with cirrhosis and overt HE when they were within 48 hours of discharge. Patients underwent cognitive tests, including Psychometric Hepatic Encephalopathy Score (PHES), and stool frequency was documented. Chart review identified Model for End-Stage Liver Disease-sodium (MELD-Na) and the presence of non-HE extrahepatic organ failures. Cox proportional hazards models were used to evaluate predictors of time to the primary composite outcome of hospital readmission for HE or death within 30 days, censoring for liver transplantation. RESULTS: Of 51 patients consented and enrolled, 14 patients met the primary composite outcome. In unadjusted Cox models, 4 variables predicted HE readmission or death: MELD-Na (hazard ratio [HR] 1.10 [1.01-1.20], P = 0.03), respiratory failure (HR 4.26 [1.47-12.35], P = 0.008), total number of HE extrahepatic organ failures (HR 1.79 [1.12-2.88], P = 0.02), and score on a PHES subtest, Number Connection Test A (per 30 seconds; HR 1.25 [1.06-1.47], P = 0.01). PHES and 24-hour stool frequency did not predict the primary outcome. When controlling for MELD-Na, respiratory failure predicted the primary outcome (HR 3.67 [1.24-10.86], P = 0.02). CONCLUSION: Cognitive testing and stool frequency at discharge did not predict poor outcomes in patients admitted with HE, while respiratory failure appeared to be a strong predictor.


Defecation , Hepatic Encephalopathy/epidemiology , Neuropsychological Tests , Female , Hepatic Encephalopathy/mortality , Hepatic Encephalopathy/psychology , Humans , Male , Patient Discharge/statistics & numerical data , Patient Readmission/statistics & numerical data , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies
4.
Front Immunol ; 9: 1244, 2018.
Article En | MEDLINE | ID: mdl-29928276

Immediate hypersensitivity reactions are induced by the interaction of allergens with specific IgE antibodies bound via FcεRI to mast cells and basophils. While these specific IgE antibodies are needed to trigger such reactions, not all individuals harboring IgE exhibit symptoms of allergy. The lack of responsiveness seen in some subjects correlates with the presence of IgG antibodies of the same specificity. In cell culture studies and in vivo animal models of food allergy and anaphylaxis such IgG antibodies have been shown to exert suppression via FcγRIIb. However, the reported absence of this inhibitory receptor on primary mast cells derived from human skin has raised questions about the role of IgG-mediated inhibition of immediate hypersensitivity in human subjects. Here, we tested the hypothesis that mast cell FcγRIIb expression might be tissue specific. Utilizing a combination of flow cytometry, quantitative PCR, and immunofluorescence staining of mast cells derived from the tissues of humanized mice, human skin, or in fixed paraffin-embedded sections of human tissues, we confirm that FcγRIIb is absent from dermal mast cells but is expressed by mast cells throughout the gastrointestinal tract. IgE-induced systemic anaphylaxis in humanized mice is strongly inhibited by antigen-specific IgG. These findings support the concept that IgG, signaling via FcγRIIb, plays a physiological role in suppressing hypersensitivity reactions.


Gene Expression Regulation , Mast Cells/immunology , Mast Cells/metabolism , Receptors, IgG/genetics , Allergens/immunology , Anaphylaxis/genetics , Anaphylaxis/immunology , Anaphylaxis/metabolism , Animals , Flow Cytometry , Humans , Hypersensitivity/genetics , Hypersensitivity/immunology , Hypersensitivity/metabolism , Immunoglobulin G/biosynthesis , Immunoglobulin G/immunology , Immunophenotyping , Mice , Mice, Transgenic , Organ Specificity/genetics , Organ Specificity/immunology , Receptors, IgG/metabolism
5.
Nat Chem ; 7(6): 489-95, 2015 Jun.
Article En | MEDLINE | ID: mdl-25991527

Artemisinin is an important antimalarial drug, but, at present, the environmental and economic costs of its semi-synthetic production are relatively high. Most of these costs lie in the final chemical steps, which follow a complex acid- and photo-catalysed route with oxygenation by both singlet and triplet oxygen. We demonstrate that applying the principles of green chemistry can lead to innovative strategies that avoid many of the problems in current photochemical processes. The first strategy combines the use of liquid CO2 as solvent and a dual-function solid acid/photocatalyst. The second strategy is an ambient-temperature reaction in aqueous mixtures of organic solvents, where the only inputs are dihydroartemisinic acid, O2 and light, and the output is pure, crystalline artemisinin. Everything else-solvents, photocatalyst and aqueous acid-can be recycled. Some aspects developed here through green chemistry are likely to have wider application in photochemistry and other reactions.


Artemisinins/chemical synthesis , Photochemical Processes , Carbon Dioxide/chemistry , Catalysis
6.
Reprod Biol Endocrinol ; 1: 16, 2003 Feb 11.
Article En | MEDLINE | ID: mdl-12646060

The response of Meishan conceptuses to an exogenous precursor for oestradiol-17beta biosynthesis was investigated in vitro, to determine whether gestational age or morphological stage of development elicit changes in hormone metabolism. Conceptuses were recovered on days 11, 12, 13 or 15 after the onset of oestrus and cultured for 6 hours at 37 degrees C, in the presence or absence of testosterone. On days 12 and 13 after the onset of oestrus spherical conceptuses were recovered from some gilts, whereas others yielded elongated or filamentous conceptuses. All conceptuses recovered on day 15 after oestrus had elongated. The number of cells per individual conceptus increased from days 11 to 13 after the onset of oestrus (P < 0.001), as did conceptus surface area (P = 0.038). Supplementing culture media with testosterone, as a substrate for oestrogen biosynthesis, significantly increased conceptus oestradiol-17beta secretion in vitro on days 12, 13 and 15, regardless of whether pre- or post-elongation conceptuses were cultured. However, on day 11 oestradiol-17beta was only detected at significant concentrations in the culture media of four testosterone supplemented conceptuses and only one gilt produced conceptuses capable of secreting oestradiol-17beta in the absence of testosterone. Therefore, the onset of conceptus oestradiol-17beta secretion is apparently limited by the expression of aromatase enzymes that are activated synchronously, irrespective of the stage of morphological development, within Meishan litters. Once established, Meishan conceptus oestradiol-17beta secretion in vitro is increased in the presence of exogenous testosterone.


Estradiol/metabolism , Swine/embryology , Animals , Aromatase/metabolism , Blastocyst/cytology , Breeding , Embryo, Mammalian/drug effects , Embryo, Mammalian/metabolism , Enzyme Induction , Female , Fetal Death/genetics , Fetal Death/physiopathology , Fetal Death/veterinary , Gestational Age , Litter Size , Organ Culture Techniques , Ovulation , Pregnancy , Testosterone/pharmacology
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