The religious topography of Dadan: sanctuaries, deities, communities

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A South-Arabian sanctuary far from home: the Minaean ‘high place’ of Jabal al-Khuraybah (north-west Arabia)

International audienceLocated on the eastern flank of the al-ʿUlā valley, in north-west Saudi Arabia, Jabal al-Khuraybah overlooks the ancient city of Dadan, which was settled from the 3rd millennium BCE to the early 1st millennium CE. In 2020, a systematic survey of this mountain was undertaken as part of the Dadan Archaeological Project (CNRS/AFALULA/RCU). During the first two seasons, a large religious complex was identified at its southern edge. It consists of a very long path, half carved, half built, which links four peaks and leads to the top of the highest one. The path is lined with nearly 400 Ancient South-Arabian inscriptions, suggesting that it was a processional path associated with the community of Minaean merchants settled at Dadan in the second half of the first millennium BCE. This paper will discuss the organisation, frequentation and chronology of this sanctuary in relation with the epigraphic finds and in the light of other mountaintop sanctuaries from North-west Arabia, the Southern Levant and South-Arabia

The organization of the cult of Ḏūġābat and its association with foreign deities: evidence from a newly discovered Dadanitic sanctuary in Jabal al-Khuraybah

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Severe but reversible impaired diaphragm function in septic mechanically ventilated patients

International audienceBackground: Whether sepsis-associated diaphragm dysfunction may improve despite the exposure of mechanical ventilation in critically ill patients is unclear. This study aims at describing the diaphragm function time course of septic and non-septic mechanically ventilated patients.Methods Secondary analysis of two prospective observational studies of mechanically ventilated patients in whom diaphragm function was assessed twice: within the 24 h after intubation and when patients were switched to pressure support mode, by measuring the endotracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Change in diaphragm function was expressed as the difference between Ptr,stim measured under pressure support mode and Ptr,stim measured within the 24 h after intubation. Sepsis was defined according to the Sepsis-3 international guidelines upon inclusion. In a sub-group of patients, the right hemidiaphragm thickness was measured by ultrasound.Results Ninety-two patients were enrolled in the study. Sepsis upon intubation was present in 51 (55%) patients. In septic patients, primary reason for ventilation was acute respiratory failure related to pneumonia (37/51; 73%). In non-septic patients, main reasons for ventilation were acute respiratory failure not related to pneumonia (16/41; 39%), coma (13/41; 32%) and cardiac arrest (6/41; 15%). Ptr,stim within 24 h after intubation was lower in septic patients as compared to non-septic patients: 6.3 (4.9–8.7) cmH 2 O vs. 9.8 (7.0–14.2) cmH 2 O ( p = 0.004), respectively. The median (interquartile) duration of mechanical ventilation between first and second diaphragm evaluation was 4 (2–6) days in septic patients and 3 (2–4) days in non-septic patients ( p = 0.073). Between first and second measurements, the change in Ptr,stim was + 19% (− 13–61) in septic patients and − 7% (− 40–12) in non-septic patients ( p = 0.005). In the sub-group of patients with ultrasound measurements, end-expiratory diaphragm thickness decreased in both, septic and non-septic patients. The 28-day mortality was higher in patients with decrease or no change in diaphragm function.Conclusion Septic patients were associated with a more severe but reversible impaired diaphragm function as compared to non-septic patients. Increase in diaphragm function was associated with a better survival

Fruitful desert: preliminary results of the archaeobotanical study of Dadan (nw Saudi Arabia)

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Non-enzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid

International audienceNeuroprostanes are lipid mediators produced by nonenzymatic free radical peroxidation of docosahex-aenoic acid (DHA). DHA is associated with a lower atherosclerosis risk, suggesting a beneficial role in cardiovascular diseases. The aim of this study was to investigate the influence of DHA peroxidation on its potentially antiarrhythmic properties (AAP) in isolated ventricular cardiomyocytes and in vivo in post-myocardial infarcted mice. Calcium imaging and biochemical experiments indicate that cardiac arrhythmias induced by isoproterenol are associated with Ca 2 þ leak from the sarcoplasmic reticulum after oxidation and phosphorylation of the type 2 ryanodine receptor (RyR2) leading to dissociation of the FKBP12.6/RyR2 complex. Both oxidized DHA and 4(RS)-4-F 4t-NeuroP prevented cellular arrhythmias and posttranslational modifications of the RyR2 leading to a stabilized FKBP12.6/RyR2 complex. DHA per se did not have AAP. The AAP of 4(RS)-4-F 4t-NeuroP was also observed in vivo. In this study, we challenged the paradigm that spontaneously formed oxygenated metabolites of lipids are undesirable as they are unconditionally toxic. This study reveals that the lipid mediator 4(RS)-4-F 4t-neuroprostane derived from nonenzymatic peroxidation of docosahexaenoic acid can counteract such deleterious effects through cardiac antiarrhythmic properties. Our findings demonstrate 4(RS)-4-F 4t-NeuroP as a mediator of the cardioprotective AAP of DHA. This discovery opens new perspectives for products of nonenzymatic oxidized ω3 polyunsaturated fatty acids as potent mediators in diseases that involve ryanodine complex destabilization such as ischemic event

Isoprostanes and neuroprostanes: Total synthesis, biological activity and biomarkers of oxidative stress in humans.

International audienceIsoprostanes (IsoPs) and neuroprostanes (NeuroPs) are formed in vivo by a free radical non-enzymatic mechanism involving peroxidation of arachidonic acid (AA, C20:4 n-6) and docosahexaenoic acid (DHA, C22:6 n-3) respectively. This review summarises our research in the total synthesis of these lipid metabolites, as well as their biological activities and their utility as biomarkers of oxidative stress in humans