Purpose: Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Methods: Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1^delTTAG/+ mice. Results: Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1^delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1^delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Conclusions: Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1^delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

Hypothermia is defined as a core body temperature below 35°C and can be caused by environmental exposure, drug intoxication, metabolic or nervous system dysfunction. This lethal pathology with medico-legal implications is complex to diagnose because macroscopic and microscopic lesions observed at the autopsy and the histological analysis are suggestive but not pathognomonic. Postmortem biochemical explorations have been progressively developed through the study of several biomarkers to improve the diagnosis decision cluster. Here, we present an updated review with novel biomarkers (such as catecholaminesO-methylated metabolites, thrombomodulin and the cardiac oxyhemoglobin ratio) as well as some propositional interpretative postmortem thresholds and, to the best of our knowledge, for the first time, we present the most adapted strategy of sampling and analyses to identify biomarkers of hypothermia. For our consideration, the most relevant identified biomarkers are urinary catecholamines and theirO-methylated metabolites, urinary free cortisol, blood cortisol, as well as blood, vitreous humor and pericardial fluid for ketone bodies and blood free fatty acids. These biomarkers are increased in response either to cold-mediated stress or to bioenergetics ketogenesis crisis and significantly contribute to the diagnosis by exclusion of death by hypothermia.

In a multicenter prospective cohort of cancer patients (CP; n = 840) and healthcare workers (HCWs; n = 935) vaccinated against COVID-19, we noticed the following: i/after vaccination, 4.4% of HCWs and 5.8% of CP were infected; ii/no characteristic was associated with post-vaccine COVID-19 infections among HCWs; iii/CP who developed infections were younger, more frequently women (NS), more frequently had gastrointestinal, gynecological, or breast cancer and a localized cancer stage; iv/CP vaccinated while receiving chemotherapy or targeted therapy had (NS) more breakthrough infections after vaccination than those vaccinated after these treatments; the opposite was noted with radiotherapy, immunotherapy, or hormonotherapy; v/most COVID-19 infections occurred either during the Alpha wave (11/41 HCW, 20/49 CP), early after the first vaccination campaign started, or during the Omicron wave (21/41 HCW, 20/49 CP), more than 3 months after the second dose; vi/risk of infection was not associated with values of antibody titers; vii/the outcome of these COVID-19 infections after vaccination was not severe in all cases. To conclude, around 5% of our CPs or HCWs developed a COVID-19 infection despite previous vaccination. The outcome of these infections was not severe.