Catalytic asymmetric conjugate addition of dialkylzinc reagents to alpha,beta-unsaturated sulfones

An efficient method is reported for the highly enantioselective copper-catalyzed conjugate addition of dialkylzinc reagents to α,β-unsaturated sulfones using a monodentate phosphoramidite ligand.

Catalytic Enantioselective Reformatsky Reaction with Aldehydes

120 years after the discovery of the Reformatsky reaction, the first effective catalytic enantioselective Reformatsky reaction with aldehydes using a binol derivative as a chiral catalyst is presented (see scheme; TMS=trimethylsilyl). The reaction is performed with ethyl iodoacetate and Me2Zn. The presence of air is found to be crucial to reach high conversions and selectivities.<br/

Mechanistic studies of the palladium-catalyzed S,O-ligand promoted C-H olefination of aromatic compounds

Pd-catalyzed C-H functionalization reactions of non-directed substrates have recently emerged as an attractive alternative to the use of directing groups. Key to the success of these transformations has been the discovery of new ligands capable of increasing both the reactivity of the inert C-H bond and the selectivity of the process. Among them, a new type of S,O-ligand has been shown to be highly efficient in promoting a variety of Pd-catalyzed C-H olefination reactions of non-directed arenes. Despite the success of this type of S,O-ligand, its role in the C-H functionalization processes is unknown. Herein, we describe a detailed mechanistic study focused on elucidating the role of the S,O-ligand in the Pd-catalyzed C-H olefination of non-directed arenes. For this purpose, several mechanistic tools, including isolation and characterization of reactive intermediates, NMR and kinetic studies, isotope effects and DFT calculations have been employed. The data from these experiments suggest that the C-H activation is the rate-determining step in both cases with and without the S,O-ligand. Furthermore, the results indicate that the S,O-ligand triggers the formation of more reactive Pd cationic species, which explains the observed acceleration of the reaction. Together, these studies shed light on the role of the S,O-ligand in promoting Pd-catalyzed C-H functionalization reactions

Dietrich Bonhoeffer as a member of the resistance and the Swedish Church. A commencement of a survey of their contacts and the resistance movement in general

The overall purpose of the essay is to initiate a survey and highlight, on the basis of sufficiently material, the dealings between Dietrich Bonhoeffer as a member of the resistance and the Swedish Church and/or its representatives. The purpose of the survey is to structure Dietrich Bonhoeffers activities in Sweden and highlight its implications. The following research questions have been used: 1: What was Dietrich Bonhoeffer doing in Sweden and what persons did he meet? 2: What was the role of the Swedish Church during the Second World War? 3: What was the impact of Dietrich Bonhoeffers visits to Sweden? In conclusion, this study of the contacts between Dietrich Bonhoeffer and the Swedish Church has shown: Dietrich Bonhoeffer was in Sweden on two occasions. He met representatives of the Swedish Church, which was engaged in issues related to ecumenism, resistance and peacework. Although the persons he met were representatives of the Swedish Church they sometimes acted as individuals with a Christian philosophy. A Philosophy I find consistent with Dietrich Bonhoeffers philosophy. The Swedish Church acted together with the Nordic folk churches during the Second World War. They were engaged in both moral and practical support of the resistance movements against Nazism. Together with representatives of the resistance movement, they came to design guidelines for an innovative. As I see it, the Swedish Church was not fully in line with the official political policy in Sweden; that Sweden was a neutral state, in order to, if possible, avoid to become directly involved in the war. One of the most provoking conclusions I have drawn is, that the opinion I had when I started my work, that Dietrich Bonhoeffers efforts in the resistance was of a decisive nature for the resistance movement as a hole, was in fact post-release constructions. I don’t mean that Dietrich Bonhoeffer didn´t contribute as a member of the resistance. But the ambiguity I have seen has created a vacuum in which his contributions are enlarged. I believe, according to this, it fully reasonable to assert these necessary corrections of the wrong interpretations and misinterpretations of Dietrich Bonhoeffers efforts. This would explain Dietrich Bonhoeffers real actions. I know that this claim can be considered controversial and imply that Dietrich Bonhoeffers status as a resistance fighter demoted. But the closer study I made of my sources, the stronger this image emerges. Although I still believe that Dietrich Bonhoeffer was a member of the resistance, the image I had of his work when I started my work on the essay has changed. A finding I think adds another dimension of Dietrich Bonhoeffer and correlations not previously observed

Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI).

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.The trial was sponsored with a Grant from Instituto de Salud Carlos III (PIE 13/00027) and a Grant from Generalitat de Catalunya (PERIS SLT/2381/2016). The sponsors have not been involved in the design, conduct, collection, analysis, interpretation of the data, nor in the preparation, review or approval of the manuscriptS

Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial

Background: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. Methods: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. Results: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94). Conclusions: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. Trial registration: ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30&nbsp;days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56\u20131.87, P&nbsp;=&nbsp;0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30&nbsp;days of surgery compared with reactive insertion