COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Unexplained bone pain and sexual addiction

International audienc

Enantiopure ferrocene-1,2-disulfoxides: synthesis and reactivity

International audienceThe rational use of directed deprotometallation, sulfur oxidation and sulfoxide/lithium exchange allowed the synthesis of enantiopure ferrocene-1,2-disulfoxide derivatives. Not only do they represent the first members of this original family, but some of them have shown promise as ligands in rhodium-catalysed conjugate addition

Butter serums and buttermilks as sources of bioactive lipids from the milk fat globule membrane: Differences in their lipid composition and potentialities of cow diet to increase n -3 PUFA

Improving the nutritional and health properties of food products, e.g. infant milk formula, by the addition offunctional ingredients is of primary importance. This study focused on bioactive milk polar lipids (PLs) recoveredfrom dietary sources that are of increasing interest. The chemical compositions of buttermilks and butterserums were determined and the modulation of the fatty acid composition of milk PLs was investigated. Butterserums contain a higher amount of milk PLs than buttermilks (88 vs. 13–18 g/kg dry matter), with a higherproportion of sphingomyelin (34 vs. 19% of PLs, respectively) interestingly close to human milk PL profile.Butter serums are also interesting sources of choline, an important nutrient for infant brain development. Wedemonstrated that the unsaturated fatty acid content of milk PLs recovered in the buttermilks and the butterserums, mainly the amount of C18:3n-3 and C22:6n-3 (DHA) that are of nutritional interest, can be increased bydietary strategies. This work opens perspectives for a better valorization of milk PLs in human nutrition (bothinfants and adults) to benefit their functional, nutritional and health properties

Contact operations using an instrumented compliant wrist

Teleprogramming was developed as a solution to problems of teleoperation systems with significant time delays [5]. In teleprogramming, the human operator interacts in real time with a graphical model of the remote site, which provides for real time visual and force feedback. The master system automatically generates symbolic commands based on the motions of the master arm and the manipulator/model interactions, given predefined criteria of what types of motions are to be expected. These commands are then sent via a communication link, which may delay the signals, to the remote site. Based upon a remote world model, predefined and possibly refined as more information is obtained, the slave carries out commanded operations in the remote world and decides whether each step has been executed correctly. Contact operations involve the remote site manipulator interacting with the environment, including planned collisions, and motion with contact with the environment. A hybrid position/force control scheme using a instrumented compliant wrist has been demonstrated to be very effective for these types of operations. In particular, switching between position and force modes (when contacting a surface, for example) does not present problems for the system. A brief introduction of teleprogramming and contact operations is presented, including a model of sliding motions and early experimental results. Problems with these earl

Ferrocenephosphonates: Copper-Promoted Synthesis and Further Functionalization

International audienceFerrocenephosphonates make up an important class of organometallic derivatives with a wide range of useful applications in organic synthesis and coordination chemistry. Here, an approach to ferro-cenephosphonates based on a copper-promoted Hirao coupling is reported. Further functionalizations based on regioselective deprotolithiation and both Negishi and Suzuki-Miyaura cross-coupling reactions are also described to reach original derivatives

Lipid droplets coated with milk fat globule membrane fragments: Microstructure and functional properties as a function of pH

Processed lipid droplets coated by milk fat globule membrane (MFGM) material are of primary interest to mimicthe specific functions provided by the fat globules in milk and dairy products. The objectiveswere to investigate,as a function of pH, the properties and microstructure ofMFGM-coated lipid droplets preparedwith an ingredientrich in MFGM containing polar lipids and proteins. The samples were prepared in water and in milk ultrafiltrate.The combination of microscopy techniques, zeta potential and particle size measurements, and rheological determinationswas used.We showed that all the components of the ingredient were highly sensitive to pH. Both thepolar lipids and proteins contributed to the isoelectric point of the MFGM-rich ingredient at pI=4.2. Lipid dropletswere coated withMFGMfragments both adsorbed at the surface of fat and protruding in the aqueous phase.BelowpH 5.5 the microstructure of the emulsions was affected by aggregation of the lipid droplets and formationof a gel. Theemulsions prepared inwater did not showcoalescence upon 30 days storage,while those prepared inmilk ultrafiltrate showed coalescence for pH below 5.5. This study demonstrates that the MFGM-rich ingredienthas excellent emulsifying properties and will contribute in the development of emulsions containing MFGMcoatedlipid droplets for techno-functional, nutritional and health benefits (e.g. in infant formulas)

Breaking the Aliphatic Wall: Iridium-Catalyzed Direct Reductive Amination of Ketones and Secondary Amines

International audienceDirect reductive amination (DRA) is a ubiquitous reaction in organic chemistry. This transformation between a carbonyl group and an amine is most often achieved using super stoichiometric amount of hazardous hydride reagents, thus being incompatible with many sensitive functional groups. DRA could also be achieved by means of chemo- or bio-catalysis, thereby attracting the interest of industry as well as academic laboratories due to their virtually perfect atomeconomy. Although DRA are well-established for substrate pairs such as aldehydes with either 1 o or 2 o amines as well as ketones with 1 o amines, the current methodologies are limited in the case of ketones with 2 o amines. Herein, we present a general DRA protocol that overcomes this major limitation by means of iridium catalysis. The applicability of the methodology is demonstrated by accessing an unprecedented range of biologically relevant tertiary amines starting from both aliphatic ketones and aliphatic amines. The choice of a disphosphane ligand (Josiphos A or Xantphos) is essential for the success of the transformation

Iridium-Catalyzed Direct Reductive Amination of Ketones and Secondary Amines: Breaking the Aliphatic Wall

International audienceInvited for the cover of this issue are Matthieu Jouffroy from Discovery Process Research at Janssen Pharmaceutica N.V. and the group of Rafael Gramage-Doria at the University of Rennes. The image depicts an Ir-based catalytic system "fueled" by hydrogen for the direct reductive amination of ketones and secondary amines, allowing complex aliphatic tertiary amines to be prepared and, so, new chemical space to be reached. Read the full text of the article at 10.1002/chem.202201078

Stereoselective ring-opening polymerization of functional β-lactones: influence of the exocyclic side-group

International audiencePolyhydroxyalkanoates (PHAs) are a unique class of polyesters especially due to their chemical diversity imparted by their side-chain substituent that provides a handle to tune their properties, such as their thermal, mechanical and (bio)degradability signature. Here, we report that some functional PHAs, namely PBPLFGs (FG = functional group), were synthesized by the controlled stereoselective ring-opening polymerization (ROP) of racemic 4-substituted-β-propiolactones, namely rac-BPLCH2ZPhs with Z = O, S, CH2OCH2, catalyzed by diamino- or amino-alkoxy-bis(phenolate) yttrium amido complexes (1a–1g) in the presence of isopropanol. Unprecedented syndio-enriched (Pr up to 0.87) PBPLCH2ZPhs of high molar mass (Mn,NMR up to 86 400 g mol−1, ĐM < 1.23) were thus typically prepared under mild operating conditions (toluene, 20 °C). Catalyst systems with smaller “uncrowded” Me or Cl ortho-substituents installed on the yttrium phenolate ligands (1a–1c) typically revealed less active than those with larger bulkier tBu or CMe2Ph groups (1d–1g), regardless of the monomer (TOF1a–1c = 0.48–15 h−1, TOF1d–1g = 450–1840 h−1). Irrespective of the catalyst system, exchanging oxygen with sulphur in BPLCH2ZPhs, with Z = O, S, did not affect the stereochemistry, always affording syndiotactic PBPLCH2ZPhs. On the other hand, either atactic or syndiotactic PBPLCH2CH2OCH2Phs were formed upon tuning the catalyst from 1a–1c or 1d–1g, respectively. The intimate relationship, through “non-covalent” interactions, between the chemical nature of the exocyclic functional side-group on the β-lactone and the stereoelectronic tuning arising from the phenolate ligand ortho-substituents within the yttrium coordination sphere, modulated the stereocontrol of the ROP. The thermal behavior of these original functional PHAs depended closely on their side-chain substituent (Tonsetd = 226 to 272 °C; Tg = −15 to +40 °C)