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1.
Marie Warrer Petersen Tine Sylvest Meyhoff Marie Helleberg Maj-Brit Nørregaard Kjær Anders Granholm Carl Johan Steensen Hjortsø Thomas Steen Jensen Morten Hylander Møller Peter Buhl Hjortrup Mik Wetterslev Gitte Kingo Vesterlund Lene Russell Vibeke Lind Jørgensen Klaus Tjelle Thomas Benfield Charlotte Suppli Ulrik Anne Sofie Andreasen Thomas Mohr Morten H. Bestle Lone Musaeus Poulsen Mette Friberg Hitz Thomas Hildebrandt Lene Surland Knudsen Anders Møller Christoffer Grant Sølling Anne Craveiro Brøchner Bodil Steen Rasmussen Henrik Nielsen Steffen Christensen Thomas Strøm Maria Cronhjort Rebecka Rubenson Wahlin Stephan Jakob Luca Cioccari Balasubramanian Venkatesh Naomi Hammond Vivekanand Jha Sheila Nainan Myatra Christian Gluud Theis Lange Anders Perner 《Acta anaesthesiologica Scandinavica》2020,64(9):1365-1375
Introduction
Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.Methods
The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.Discussion
The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.2.
Kristina A. Theis Louise Murphy Jennifer M. Hootman Charles G. Helmick Edward Yelin 《Arthritis care & research》2007,57(3):355-363
Objective
To estimate the national prevalence of arthritis‐attributable work limitation (AAWL) among persons ages 18–64 with doctor‐diagnosed arthritis and examine correlates of AAWL.Methods
Using the 2002 National Health Interview Survey, we estimated the prevalence of AAWL (limited in whether individuals work, the type of work they do, or the amount of work they do) and correlates of AAWL in univariable and multivariable‐adjusted logistic regression analyses. Survey data were analyzed in SAS and SUDAAN to account for the complex sample design.Results
A total of 5.3% of all US adults ages 18–64 reported AAWL; in this age group, AAWL is reported by ~30% of those who report arthritis. The prevalence of AAWL was highest among people ages 45–64 years (10.2%), women (6.3%), non‐Hispanic blacks (7.7%), people with less than a high school education (8.6%), and those with an annual household income <$20,000 (12.6%). AAWL was substantially increased among people with arthritis‐attributable activity limitations (multivariable‐adjusted odds ratio [OR] 9.1, 95% confidence interval [95% CI] 7.1–11.6). The multivariable‐adjusted likelihood of AAWL was moderately higher among non‐Hispanic blacks (OR 1.6, 95% CI 1.2–2.3), Hispanics (OR 1.8, 95% CI 1.2–2.6), and people with high levels of functional/social/leisure limitations (OR 1.8, 95% CI 1.4–2.3) and was decreased among those with a college education (OR 0.6, 95% CI 0.4–0.8).Conclusion
AAWL is highly prevalent, affecting millions of Americans and one‐third of adults with doctor‐diagnosed arthritis. Findings suggest the need for more targeted research to better understand the natural history, success of interventions, and effects of policy on AAWL. Public health interventions, including self‐management education programs, may be effective in countering AAWL. 相似文献3.
The new thromboxane A2 antagonist [3H]BAY U 3405 was characterized for its binding to washed human platelets and platelet membranes. In washed platelets the specific binding was reversible, selective and stereospecific, but not saturable. The dissociation constant (Kd) was 6 +/- 2.5 nM, the number of specific binding sites 1177 +/- 306 per platelet. Three structurally different thromboxane A2 (TXA2)/prostaglandin H2 (prostaglandin endoperoxide) (PGH2) receptor ligands completely inhibited the specific binding of [3H]BAY U 3405 in a concentration-dependent manner, indicating that the observed high affinity binding site is the TXA2/PGH2 receptor. In platelet membranes, however, specific [3H]BAY U 3405 binding showed saturability in addition to reversibility, selectivity, and stereospecifity. The Kd of the binding was 9.6 +/- 2.3 nM in kinetic studies and 8.7 +/- 3.7 nM in saturation studies, the inhibition constant (Ki) was 10 +/- 1.1 nM in displacement studies. The TXA2/PGH2 receptor agonists U 46619 and CTA2, and the antagonists Daltroban (BM 13505), I-PTA-OH and SQ 29548 all completely inhibited the specific binding of [3H]BAY U 3405 thus defining the observed binding site as the TXA2/PGH2 receptor. In conclusion, the data suggest that the previously reported TXA2 antagonism of BAY U 3405 is mediated by binding to a specific high affinity binding site of human platelets and platelet membranes that represents the TXA2/PGH2 receptor. 相似文献
4.
5.
Otto C Gasser M Waaga-Gasser AM Rohde AC Lenhard M Jost S Gassel HJ Ulrichs K Timmermann W 《Human immunology》2002,63(10):880-887
It has been extensively documented the role of the indirect pathway of allorecognition in allograft rejection. However, recent data demonstrate that the manipulation of this pathway could be also sufficient to promote prolongation of allograft survival. In the present study we evaluated the effect of preoperative immunization with the WF-specific MHC class II peptides RT1.D2 and RT1.B2 in combination with low-dose CsA from days 0 to 7 (5 mg/kg/day) and from days 8 to 30 (1 mg/kg/day) after WF small bowel transplantation. Seven days before and on the day of transplantation, LEW recipients were immunized with the two WF MHC class II peptides RT1.B2 and RT1.D2. The CsA monotherapy induced an allograft survival of 49.3 +/- 6.1 days. MHC class II peptide immunization had a limited effect on allograft survival for RT1.D2 (47.1 +/- 3.8 days) and induced prolongation of allograft survival for RT1.B2 (73.6 +/- 34.6 days). This effect seems to be based on the absence or silence of RT1.B2-reactive T cells and rejection seems to be correlated with the presence of RT1.B2-specific T cells in the late phase. Therefore, the combination of RT1.B2 with low-dose CsA shifts the immunological response and protects small bowel allograft rejection. 相似文献
6.
Solid mesoionic 2‐[2‐(isopropenylcarbonyloxy)ethylthio]‐1‐methyl‐6‐oxo‐3‐phenyl‐5‐propyl‐1,6‐dihydropyrimidin‐3‐ium‐4‐olate was complexed in water using β‐cyclodextrin (β‐CD) and randomly methylated β‐CD, which resulted in polymerizable complexes with 2:1 stoichiometry. The β‐CD complex was characterized using 1H NMR, ROESY NMR and UV spectroscopy. Polymerization of the complex prepared from methylated β‐CD led to a photosensitive polymer, which precipitated during polymerization and was nearly free of CD. Polymerization was carried out with a water‐soluble redox initiator. In addition, a copolymer with methyl methacrylate was prepared from the complexes, which showed a different mass‐dependent distribution in the incorporation in comparison to a copolymer prepared without CD in organic solvents.
7.
Franka Neumer Orenci Urraca Joaquin Alonso Jesús Palencia Vicente Varea Stephan Theis Maria Rodriguez-Palmero Jos Antonio Moreno-Muoz Francisco Guarner Gigi Veereman Yvan Vandenplas Cristina Campoy 《Nutrients》2021,13(4)
The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections. 相似文献
8.
Subpopulations of suppressor cells in chickens infected with cells of a transplantable lymphoblastic leukemia. 下载免费PDF全文
G A Theis 《Infection and immunity》1981,34(2):526-534
Three distinct subpopulations of cells with suppressor activity were separated by Ficoll density gradient centrifugation methods from the spleens of 3- to 4- week-old chickens infected with cultured lymphoblastoid cells (JM-VLC), derived from JM-V leukemia: (i) a subpopulation of nonadherent cells, which separated in the T-cell-rich gradient fraction of leukemic chicken spleen, inhibited proliferative responses to concanavalin A in mixed cultures with normal chicken spleen cells; (ii) phagocytic cells (macrophages), which were the most effective suppressor cells of all subpopulations in the mixed culture assay, were recovered among the cells of greatest density in the spleens of both normal and leukemic chickens; (iii) JM-VLC cells in the buoyant gradient fractions of leukemic chicken spleens also effected suppression. In the later stages of lymphoproliferative disease, the number of spleen cells of buoyant density was increased, apparently as a result of infiltration of the spleens with JM-VLC cells. 相似文献
9.
Muhammad Daud Prasad Dasari Marion Adelfinger Daniela Langenhorst Jasmin Lother Dragana Slavkovic-Lukic Carsten Berges Michaela Kruhm Annette Galler Cathrin Schleussner Christian H. Luther Karl Alberter Anton Althammer Haroon Shaikh Niklas Pallmann Jochen Bodem Mohammed El-Mowafy Andreas Beilhack Marcus Dittrich Max S. Topp Peter F. Zipfel Niklas Beyersdorf 《European journal of immunology》2023,53(11):2250284
To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4+ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4+ T-cell recall responses. Therapeutically, CD4+ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4+ T cells with CaEno1 modulated host CD4+ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4+ T-cell responses. 相似文献
10.
Certain delivery systems are intended to release the active ingredient in different phases to obtain the desired therapeutic effect. For these formulations, such as a bilayer tablet, it is desirable to distinguish and measure the release of drug from the different phases simultaneously. Mass spectrometric methods were developed to measure three ibuprofen isotopomers in serum and two in dissolution fluid. The analytical methods were linear (r 0.992) over the concentration range of interest and recovery was greater than 99.2% for all isotopomers. Coadministration of [2H0]ibuprofen, [2H4]ibuprofen, and [2H7]ibuprofen to male beagles demonstrated that the isotopomers were bioequivalent and verified the absence of any kinetic isotope effect due to deuterium incorporation (p = 0.286). These methods were then used to evaluate a bilayer tablet formulation composed of an immediate release layer of 100 mg [2H4]ibuprofen and a sustained release layer with a drug load of 300 mg [2H0]ibuprofen. Two different rate-controlling polymer matrices that provided similar in vitro dissolution profiles were compared in the sustained release phase, while the immediate release formulation remained the same. In male beagles, the HPMC matrix delivered a significantly greater amount of ibuprofen (p < 0.05). The AUC was threefold greater for HPMC (1067 ± 437 nmole * h/ml) versus EUDRAGIT® (320 ± 51), and Cmax was nearly four times greater (145 ± 62.1 nmole/ml for HPMC versus 37.9 ± 14.4 for EUDRAGIT®). Although Tmax for HPMC (3.4 ± 1.9 h) lagged behind EUDRAGIT® (2.0 ± 0.82 h), the difference was not significant (p > 0.05). The immediate release layer was absorbed to the same extent as an oral solution (containing [2H7]ibuprofen) that was administered concomitantly with the bilayer tablet. Using the stable isotope markers also demonstrated that the release rates of the two layers were independent of each other, both in vivo and in vitro. Stable isotope techniques are a useful tool in the development of biphasic release formulations since they can be used to determine proper drug load of each phase as well as the appropriate rate of release. 相似文献