174 research outputs found
The Role of Dynamic Ligand Exchange in the Oxidation Chemistry of Cerium(III)
The CeIII/IV couple is useful for many applications in organic, inorganic, and materials chemistry. However, attaining a general method to access both oxidations states through reversible solution redox chemistry remains challenging. Herein we report the synthesis, characterization, and oxidation chemistry of the novel Ce/Li REMB heterochiral diastereomer, 1-Ce(het). The solution exchange processes of 1-RE(het) (RE ΒΌ Ce and Yb) were investigated to estimate rates of ligand and cation exchange relevant in homochiral and heterochiral frameworks. A detailed mechanistic investigation following the solution dynamics of 1-Ce(het) revealed reactivity controlled both by ligand reorganization and redistribution processes. Ligand reorganization was responsible for the kinetics associated with the chemical oxidation reaction, whereas ligand redistribution and exchange dictated the isolated product
Efficacy and safety outcomes of recanalization procedures in patients with acute symptomatic pulmonary embolism: systematic review and network meta-analysis.
Background We aimed to review the efficacy and
safety of recanalisation procedures for the treatment of
PE.
Methods We searched PubMed, the Cochrane
Library, EMBASE, EBSCO, Web of Science and CINAHL
databases from inception through 31 July 2015 and
included randomised clinical trials that compared the
effect of a recanalisation procedure versus each other or
anticoagulant therapy in patients diagnosed with PE. We
used network meta-analysis and multivariate randomeffects
meta-regression to estimate pooled differences
between each intervention and meta-regression to
assess the association between trial characteristics and
the reported effects of recanalisation procedures versus
anticoagulation.
Results For all-cause mortality, there were no
significant differences in event rates between any of the
recanalisation procedures and anticoagulant treatment
(full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01;
low-dose thrombolysis: 0.47; 95%CI 0.14 to 1.59; and
catheter-associated thrombolysis: 0.31; 95%CI 0.01 to
7.96). Full-dose thrombolysis increased the risk of major
bleeding (2.00; 95%CI 1.06 to 3.78) compared with
anticoagulation. Catheter-directed thrombolysis was
associated with the lowest probability of dying (surface
under the cumulative ranking curve (SUCRA), 0.67),
followed by low-dose thrombolysis (SUCRA, 0.66) and
full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose
thrombolysis was associated with the lowest probability
of major bleeding (SUCRA, 0.61), followed by catheterdirected
thrombolysis (SUCRA, 0.54) and full-dose
thrombolysis (SUCRA, 0.17). The results were similar in
sensitivity analyses based on restricting only to studies in
haemodynamically stable patients with PE.
Conclusions In the treatment of PE, recanalisation
procedures do not seem to offer a clear advantage
compared with standard anticoagulation. Low-dose
thrombolysis was associated with the lowest probability
of dying and bleedingpre-print549 K
Emotional WellβBeing of Living Kidney Donors: Findings From the RELIVE Study
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109345/1/ajt12906.pd
Glutathione de Novo Synthesis but Not Recycling Process Coordinates with Glutamine Catabolism to Control Redox Homeostasis and Directs Murine T Cell Differentiation
Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamateβcysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis dampened the pathological progression of experimental autoimmune encephalomyelitis (EAE). We further reveal that glutamine provides essential precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism fuels de novo synthesis of GSH and directs the lineage choice in T cells
Several clinical interests regarding lung volume reduction surgery for severe emphysema: meta-analysis and systematic review of randomized controlled trials
<p>Abstract</p> <p>Objectives</p> <p>We aim to address several clinical interests regarding lung volume reduction surgery (LVRS) for severe emphysema using meta-analysis and systematic review of randomized controlled trials (RCTs).</p> <p>Methods</p> <p>Eight RCTs published from 1999 to 2010 were identified and synthesized to compare the efficacy and safety of LVRS vs conservative medical therapy. One RCT was obtained regarding comparison of median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS). And three RCTs were available evaluating clinical efficacy of using bovine pericardium for buttressing, autologous fibrin sealant and BioGlue, respectively.</p> <p>Results</p> <p>Odds ratio (95%CI), expressed as the mortality of group A (the group underwent LVRS) versus group B (conservative medical therapies), was 5.16(2.84, 9.35) in 3 months, 3(0.94, 9.57) in 6 months, 1.05(0.82, 1.33) in 12 months, respectively. On the 3<sup>rd</sup>, 6<sup>th </sup>and 12<sup>th </sup>month, all lung function indices of group A were improved more significantly as compared with group B. PaO2 and PaCO2 on the 6<sup>th </sup>and 12<sup>th </sup>month showed the same trend. 6MWD of group A on the 6<sup>th </sup>month and 12<sup>th </sup>month were improved significantly than of group B, despite no difference on the 3<sup>rd </sup>month. Quality of life (QOL) of group A was better than of group B in 6 and 12 months. VATS is preferred to MS, due to the earlier recovery and lower cost. And autologous fibrin sealant and BioGlue seems to be the efficacious methods to reduce air leak following LVRS.</p> <p>Conclusions</p> <p>LVRS offers the more benefits regarding survival, lung function, gas exchange, exercise capacity and QOL, despite the higher mortality in initial three postoperative months. LVRS, with the optimization of surgical approach and material for reinforcement of the staple lines, should be recommended to patients suffering from severe heterogeneous emphysema.</p
Development of a Humanized HLA-A2.1/DP4 Transgenic Mouse Model and the Use of This Model to Map HLA-DP4-Restricted Epitopes of HBV Envelope Protein
A new homozygous humanized transgenic mouse strain, HLA-A2.1+/+HLA-DP4+/+ hCD4+/+mCD4β/βIAΞ²β/βΞ²2mβ/β (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2+/+Ξ²2mβ/β (A2) mouse and our previously created HLA-DP4+/+ hCD4+/+mCD4β/βIAΞ²β/β (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans
A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses
Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus
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