Insight into the conformational space of n-benzyl-n-(furan-2-ylmethyl) acetamide by NMR spectroscopy and DFT calculations

In this study, the conformational behavior of N-benzyl-N-(furan-2-ylmethyl) acetamide in chloroform was addressed by using a combined experimental/theoretical strategy using NMR spectroscopy and quantum chemical calculations. The 1H and 13C one-dimensional NMR spectra, as well as the two-dimensional HSQC-DEPT and HMBC-DEPT NMR spectra, evinced the presence of a hindered cis(E)-trans(Z) rotational equilibrium in solution. DFT calculations were performed at different theoretical levels using the polarizable continuum model (PCM) and predicted nine (four Z and five E structures) stable conformations. The interconversion dynamics among the different confirmations were established in terms of four different rotational equilibria in CDCl3. The chemical shifts in the 1H and 13C NMR spectra of the compound are similar to the values calculated for the two most abundant conformational equilibria at room temperature, one caused by two Z rotamers and the other by two E rotamers. The compound was also characterized for the first time by FTIR, Raman spectroscopy, and GC/MS spectrometry. Additionally, several acylation methodologies for synthesizing the title compound from N-benzyl-1-(furan-2-yl)methanamine were tested which resulted in high yields (> 90%) under very convenient conditions (10 min, at room temperature).Fil: Corredor Montaña, Jeisson D.. Universidad Pedagógica y Tecnológica de Colombia; ColombiaFil: Loaiza, Alix. Pontificia Universidad Javeriana; ColombiaFil: Romanelli, Gustavo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; ArgentinaFil: de Waele, Isabelle. University Of Lille.; FranciaFil: Tobón Correa, Yeny Alexandra. University Of Lille.; FranciaFil: Gomez Castaño, Jovanny Arles. Universidad Pedagógica y Tecnológica de Colombia; Colombi

A Cell Wall Proteome and Targeted Cell Wall Analyses Provide Novel Information on Hemicellulose Metabolism in Flax

International audienceExperimentally-generated (nanoLC-MS/MS) proteomic analyses of four different flax organs/tissues (inner-stem, outer-stem, leaves and roots) enriched in proteins from 3 different sub-compartments (soluble-, membrane-, and cell wall-proteins) was combined with publically available data on flax seed and whole-stem proteins to generate a flax protein database containing 2996 nonredundant total proteins. Subsequent multiple analyses (MapMan, CAZy, WallProtDB and expert curation) of this database were then used to identify a flax cell wall proteome consisting of 456 nonredundant proteins localized in the cell wall and/or associated with cell wall biosynthesis, remodeling and other cell wall related processes. Examination of the proteins present in different flax organs/tissues provided a detailed overview of cell wall metabolism and highlighted the importance of hemicellulose and pectin re-modeling in stem tissues. Phylogenetic analyses of proteins in the cell wall proteome revealed an important paralogy in the class IIIA xyloglucan endo-transglycosy-lase/hydrolase (XTH) family associated with xyloglucan endo-hydrolase activity. Immunolocalisation, FT-IR microspectroscopy, and en-zymatic fingerprinting indicated that flax fiber primary/S1 cell walls contained xyloglucans with typical substituted side chains as well as glucuronoxylans in much lower quantities. These results suggest a likely central role of xyloglucans and endotransglucosylase/hydrolase activity in flax fiber formation and cell wall remodeling processes. Molecular & Cellula

Insight into the conformational space of n-benzyl-n-(furan-2-ylmethyl)acetamide by NMR spectroscopy and DFT calculations

In this study, the conformational behavior of N-benzyl-N-(furan-2-ylmethyl) acetamide in chloroform was addressed by using a combined experimental/theoretical strategy using NMR spectroscopy and quantum chemical calculations. The 1H and 13C one‑dimensional NMR spectra, as well as the two-dimensional HSQC-DEPT and HMBC-DEPT NMR spectra, evinced the presence of a hindered cis(E)-trans(Z) rotational equilibrium in solution. DFT calculations were performed at different theoretical levels using the polarizable continuum model (PCM) and predicted nine (four Z and five E structures) stable conformations. The interconversion dynamics among the different confirmations were established in terms of four different rotational equilibria in CDCl3. The chemical shifts in the 1H and 13C NMR spectra of the compound are similar to the values calculated for the two most abundant conformational equilibria at room temperature, one caused by two Z rotamers and the other by two E rotamers. The compound was also characterized for the first time by FTIR, Raman spectroscopy, and GC/MS spectrometry. Additionally, several acylation methodologies for synthesizing the title compound from N-benzyl-1-(furan-2-yl)methanamine were tested which resulted in high yields (> 90%) under very convenient conditions (10 min, at room temperature).Centro de Investigación y Desarrollo en Ciencias Aplicada

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: A descriptive analysis of the Eurobact II study

Background: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Modulation des propriétés intrinsèques et neurochimiques des motoneurones faciaux après axotomie

L axotomie du nerf facial est un bon modèle d étude de la plasticité neuronale dans le système nerveux périphérique. Durant les 2 premiers mois après lésion, l expression des ARNm codant les 3 sous-unités des canaux potassiques calcium-dépendant (SKi-3) et la sous-unité auxiliaire 31 des canaux sodiques voltage-dépendant est modifiée. La lésion modifie aussi sévèrement les propriétés neurochimiques des motoneurones. Les sous-unités majeures des récepteurs au GABA (GABAA CL1, 132 et y2 GABAB lb et 2) et au glutamate de type AMPA (GIuR2-4) sont fortement diminuées tant au niveau transcriptionnel que traductionnel. Ces résultats sont en accord avec l hypothèse selon laquelle, en réponse à une lésion, les motoneurones diminuent l expression des molécules dévolues à la transmission synaptique au profit de celles impliquées dans la régénération axonale. Le blocage d un facteur rétrograde périphérique, e silence neuronal, un signal lésionnel pourraient faire partie des signaux déclenchant.Facial nerve axotomy is a good model for studying neuronal plasticity in the peripheral nervous system. During the first 2 months after lesion, the expression pattern ol mRNA coding the 3 subunits of Ca2 activated K channel (SKi-3) and the f31 auxiliar subunit of the voltage-dependent sodium channels is modified. The lesion also severely modifies the neurochemical properties of the motoneurons. Major subunits of the GABI receptors (GABAA cLl, f32 and 2; GABAB lb and 2) and AMPA glutamate receptors (GIuR2-4) are strongly decreased as well at the level of mRNA and protein. These results are in agreement with the hypotheses according to which, in response to a lesion, the motoneurons decrease the expression of the molecules reserved for the synaptic transmission with the profit of those mplied in axonal regeneration. The blocking of a peripheral factor, the neuronal silence or an injury signal could be implied in these modulations.PARIS5-BU Saints-Pères (751062109) / SudocSudocFranceF

Hot-Electron Photodynamics of Silver-Containing Nanosized Zeolite Films Revealed by Transient Absorption Spectroscopy

Accessed by 12/2017International audienc