Effects of endotoxin on lactate metabolism in humans.

ABSTRACT: INTRODUCTION: Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge. METHODS: Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose. RESULTS: In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged. CONCLUSIONS: LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production. TRIAL REGISTRATION: ClinicalTrials.gov NCT01647997

Troubles dépressifs traités par thérapie cognitivo-comportementale effectuée par des infirmiers spécialisés en corrélation avec le retour au travail: travail de Bachelor

Cette revue de littérature a pour objectif de comprendre comment une thérapie cognitivo-comportementale permet de soigner les troubles dépressifs tout en proposant un retour au travail. Le but est de promouvoir les bienfaits des traitements non-médicamenteux sur des personnes souffrant de troubles dépressifs qui influent sur leur carrière professionnelle ou, se retrouvant au chômage à cause de ceux-ci, à travers la vision des soins élaborée par Martha Rogers dans sa théorie visant au bien-être

Photocatalytic Barbier Reaction – Visible-Light induced Allylation and Benzylation of Aldehydes and Ketones

We report a photocatalytic version of the Barbier type reaction using readily available allyl or benzyl bromides and aromatic aldehydes or ketones as starting materials to generate allylic or benzylic alcohols. The reaction proceeds at room temperature under visible light irradiation with the organic dye 3,7-di(4-biphenyl)1-naphthalene-10-phenoxazine as a photocatalyst and DIPEA as sacrificial electron donor. The proposed cross-coupling mechanism of a ketyl- and an allyl or benzyl radical is supported by spectroscopic investigations and cyclic voltammetry measurements

ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains as well as 3-D protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature, and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB) announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2,000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology [ISMB] 2016, Orlando, Florida)

Innovative diagnostic methods to detect harmful wood-inhabiting insects

Eine nicht-invasive Diagnose holzzerstörender Schadorganismen ist von großer Bedeutung um Eingriffe in kostbare Holzprodukte und lebende Bäume auf ein Minimum zu beschränken. Hier stellen wir zwei ganz unterschied­liche Methoden vor, eine physikalische und eine molekularbiologische, die einen schonenden Nachweis von Insekten­larven im Holz ermöglichen. Beide Methoden sind bereits zum Teil erfolgreich zur Analyse des Asiatischen Laubholzbockkäfers (Anoplophora glabripennis, ALB) eingesetzt worden und eignen sich als Frühwarnsysteme in der Bekämpfung von Quarantäneschadinsekten.Non-invasive diagnosis of harmful wood-inhabiting orga­nisms is of great importance in order to minimize interventions in valuable wood products and living trees. Here we present two methods, an acoustical and a molecular one, which enable gentle detection of insect larvae in wood and wood products. In parts, both methods have been successfully applied for the analysis of the Asian longhorn beetle (Anoplophora glabripennis, ALB) and appear suitable as early warning systems in the control of quarantine insect pests

Photocarboxylation of Benzylic C-H bonds

The carboxylation of sp(3)-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy

Photocatalytic Carbanion Generation – Benzylation of Aliphatic Aldehydes to Secondary Alcohols

We present a redox-neutral method for the photocatalytic generation of carbanions. Benzylic carboxylates are photooxidized by single electron transfer; immediate CO2 extrusion and reduction of the in situ formed radical yields a carbanion capable of reacting with aliphatic aldehydes as electrophiles giving the Grignard analogous reaction product

Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects

Objective: To assess the effects of intravenous fish oil fat emulsion on the metabolic alterations induced by lipopolysaccharide (LPS) challenge in healthy volunteers. Design: Two groups of eight healthy subjects were randomized to receive either two pharmacological doses of intravenous FO fat emulsion or no treatment. The FO group received twice 0.5 g/kg 10% emulsion (Omegaven) 48 and 24 h before investigation. LPS (2 ng/kg) was injected as abolus on the investigation day. Systemic parameters, indirect calorimetry, heart rate variability, and platelet membrane phospholipid composition were measured. Results: Basal EPA and DHA content in platelet phospholipids was low (0.28% and 2.54%, respectively) and increased significantly after FO to 1.68% and 3.32%. LPS induced reproducible effects in all subjects. Fever was higher in the FO group than in controls; the difference was significant from t 120 until t 360. FO blunted the neuroendocrine response: the rise in plasma norepinephrine was sevenfold lower at t 120 while the ACTH peak was fourfold lower. Tumor necrosis factor α was significantly lower between t 360 and t 180 in the FO group. Conclusions: Two doses of intravenous FO fat emulsion modified the phospholipid composition of platelets in healthy subjects. FO blunted fever and increased the neuroendocrine and the inflammatory responses to LP

Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a long-term, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients