4D electron tomography of dislocations undergoing electron irradiation

Imaging dislocation microstructures in 3D and monitoring their interactions over time is a major challenge. In this study, we show that enhancing the contrast of dislocation lines prior to reconstruction, allows to optimize an acquisition phase with fewer images and thus to follow the 3D evolution of a microstructure over time. We illustrate this new possibility by studying the first stages of formation of helical dislocations in MgO under electron irradiation. We highlight the role of segment mobility on the initiation of climb and reveal the existence of preferential mixed climb planes

Is a Calorie Really a Calorie? Metabolic Advantage of Low-Carbohydrate Diets

The first law of thermodynamics dictates that body mass remains constant when caloric intake equals caloric expenditure. It should be noted, however, that different diets lead to different biochemical pathways that are not equivalent when correctly compared through the laws of thermodynamics. It is inappropriate to assume that the only thing that counts in terms of food consumption and energy balance is the intake of dietary calories and weight storage. Well-controlled studies suggest that calorie content may not be as predictive of fat loss as is reduced carbohydrate consumption. Biologically speaking, a calorie is certainly not a calorie. The ideal weight loss diet, if it even exists, remains to be determined, but a high-carbohydrate/low-protein diet may be unsatisfactory for many obese individuals

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Hardening mechanisms in olivine single crystal deformed at 1090 degrees C: an electron tomography study

International audienc

Severe Keratitis Caused by Pseudomonas aeruginosa Successfully Treated with Ceftazidime Associated with Acetazolamide

Purpose. To report a case of microbial keratitis caused by Pseudomonas aeruginosa treated with a combination of acetazolamide and ceftazidime. Methods. Case report. Results. We report the case of a 17-year-old contact lens-wearing female who developed severe keratitis due to Pseudomonas aeruginosa temporarily healed with topical fortified antibiotic eye drops. After few days, the patient relapsed, and topical and intravenous ceftazidime were added. Concomitantly, oral administration of acetazolamide was prescribed. This carbonic anhydrase inhibitor was added to the antibiotic regimen in order to decrease the anterior chamber pH, and then, the ceftazidime ionization. By lowering the state of ionization of the antibiotic in the aqueous humor, its concentration was increased. This was confirmed by an improvement of the patient within few days and a rapid eradication of the infection. Conclusion. This is the first reported case of keratitis caused by P. aeruginosa successfully treated using acetazolamide as an enhancer of ceftazidime effectiveness

Comment on: Antiepileptic prescribing to persons living with dementia residing in nursing homes: A tale of two indications

International audienceNo abstract availabl

The collaboration of clinical pharmacists and physicians for medication safety

International audienc

Beyond AICA riboside: In search of new specific AMP-activated protein kinase activators.

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICA riboside) has been extensively used in vitro and in vivo to activate the AMP-activated protein kinase (AMPK), a metabolic sensor involved in both cellular and whole body energy homeostasis. However, it has been recently highlighted that AICA riboside also exerts AMPK-independent effects, mainly on AMP-regulated enzymes and mitochondrial oxidative phosphorylation (OXPHOS), leading to the conclusion that new compounds with reduced off target effects are needed to specifically activate AMPK. Here, we review recent findings on newly discovered AMPK activators, notably on A-769662, a nonnucleoside compound from the thienopyridone family. We also report that A-769662 is able to activate AMPK and stimulate glucose uptake in both L6 cells and primary myotubes derived from human satellite cells. In addition, A-769662 increases AMPK activity and phosphorylation of its main downstream targets in primary cultured rat hepatocytes but, by contrast with AICA riboside, does neither affect mitochondrial OXPHOS nor change cellular AMP:ATP ratio. We conclude that A-769662 could be one of the new promising chemical agents to activate AMPK with limited AMPK-independent side effects. (c) 2008 IUBMB IUBMB Life, 2008

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation.

AMP-activated protein kinase (AMPK) controls glucose uptake and glycolysis in muscle. Little is known about its role in liver glucose uptake, which is controlled by glucokinase. We report here that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and inhibited glucose phosphorylation and glycolysis in rat hepatocytes. In vitro experiments demonstrated that this inhibition was not due to direct phosphorylation of glucokinase or its regulatory protein by AMPK. By contrast, AMPK phosphorylated liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase without affecting activity. Inhibitors of the endothelial nitric oxide synthase, stress kinases, and phosphatidylinositol 3-kinase pathways did not counteract the effects of AICAR, metformin, or oligomycin, suggesting that these signaling pathways were not involved. Interestingly, the inhibitory effect on glucose phosphorylation of these well-known AMPK activators persisted in primary cultured hepatocytes from newly engineered mice lacking both liver alpha1 and alpha2 AMPK catalytic subunits, demonstrating that this effect was clearly not mediated by AMPK. Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose-induced translocation of glucokinase from the nucleus to the cytosol by a mechanism that could be related to the decrease in intracellular ATP concentrations observed in these conditions