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The main purpose of this study was to identify and analyze the prevailing types of accidents at roundabouts. The relationship was revealed between certain types of accidents, the place of their occurrence, and the configuration of the roundabout. The study analyzed 321 accidents at 19 ring intersections. Four predominant crash types were identified: rear-end collision, collision with vulnerable road users, side swipe collision, and entering circulate collision. The greatest number of accidents occurred at the weaving lane and at the entrances and exits of the roundabout. Dividing the ring intersections into separate sections to determine the location of the accident allows drawing conclusions on the nature of road traffic accidents and the impact of the roundabout design on safety.

Background: Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms-CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium- dependent and - independent responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined., Methods: 94 men were included: 18 lowlanders (LL), 38 healthy highlanders permanently living at 3800 m (n = 21-HL-3800) or in La Rinconada, the highest city in the world (5100-5300 m) (n = 17-HL-5100/No CMS). Moreover, 14 participants with mild (Mild CMS) and 24 with moderate to severe CMS (Mod/Sev CMS) were recruited. All undertook two reactivity tests: i) local thermal hyperaemia (microcirculation) and ii) flow-mediated dilation (macrocirculation). Endothelium- independent function (glyceryl trinitrate) was also assessed only in La Rinconada., Findings: Conductance and skin blood flow velocity during the microcirculation test, as well as macrocirculation progressively decreased with altitude (LL > HL-3800 > HL-5100/No CMS). CMS also induced a decrease in macrocirculation (HL-5100/No CMS > Mild CMS = Mod/Sev CMS), while glyceryl trinitrate restored vascular function. Both oxidative stress and nitric oxide metabolites increased with altitude only. Principal component analysis revealed that increasing inflammation with altitude was associated with a progressive decline in both micro- and macrovascular function in healthy highlanders., Interpretation: Both micro and macrovascular function are affected by chronic exposure to hypoxia, the latter being further compounded by CMS., Funding: The "Fonds de dotation AGIR pour les maladies chroniques", the "Air Liquide Foundation", and the "French National Research Agency"., Competing Interests: None., (© 2024 The Authors.)

Louis, Alexandre, Charlotte Pröpper, Yann Savina, Corentin Tanne, Guy Duperrex, Paul Robach, Pascal Zellner, Stéphane Doutreleau, Jean-Michel Boulet, Alain Frey, Fabien Pillard, Cristina Pistea, Mathias Poussel, Thomas Thuet, Jean-Paul Richalet, and François Lecoq-Jammes. The impact of COVID-19 on the response to hypoxia. High Alt Med Biol . 24:321-328, 2023. Background: Severe high-altitude illness (SHAI) and coronavirus disease 2019 (COVID-19), while differing in most aspects of pathophysiology, both involve respiratory capacity. We examined the long-term impact of COVID-19 on response to hypoxia in individuals free of symptoms but having tested positive during the pandemic. The need for recommendations for such individuals planning a stay at high altitude are discussed. Methods: This multicenter study recruited participants from the multiSHAI cohort, all of whom had previously undergone a hypoxic exercise test. These participants were classified into two groups depending on whether they had since suffered mild-to-moderate COVID-19 (COVID+) or not (Control) and then asked to retake the test. Primary outcomes were: desaturation induced by hypoxia at exercise (ΔSpE), hypoxic cardiac response at exercise, hypoxic ventilatory response at exercise, and SHAI risk score. Results: A total of 68 participants retook the test, 36 classified in the COVID+ group. Analyses of primary outcomes showed no significant differences between groups. However, the COVID+ group showed significantly increased ventilation (VE) parameters during both hypoxic ( p  = 0.003) and normoxic exercise ( p  = 0.007). However, only the VE/oxygen consumption relationship during hypoxic exercise was significantly different. Conclusion: This study demonstrates no negative impact of COVID-19 on response to hypoxia as evaluated by the Richalet test. Clinical Trial Registration: NTC number: NCT05167357.

Objective: Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing., Methods: We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization., Results: uPAR-/- mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR-/- mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution., Conclusion: This study suggests that excisional wounds in uPAR-/- mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The impact of the local inhibition of soluble epoxide hydrolase, which metabolizes vasodilator and anti-inflammatory epoxyeicosanoids, on diabetic skin microvascular dysfunction was assessed. In diabetic db/db mice, basal skin blood flow assessed using laser Doppler imaging was similar to that of control mice, but thermal hyperemia was markedly reduced. At 2 h after the topical administration of an aqueous gel containing the soluble epoxide hydrolase inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB: 400 mg/L), the peak concentration of t-AUCB was detected in the skin of diabetic mice, which quickly decreased thereafter. In parallel, 2 h after application of t-AUCB treatment, thermal hyperemia was increased compared to the control gel. Quantification of t-AUCB in plasma of treated animals showed no or low systemic diffusion. Furthermore, haematoxylin and eosin histological staining of skin biopsies showed that skin integrity was preserved in t-AUCB-treated mice. Finally, for pig ear skin, a surrogate for human skin, using Franz diffusion cells, we observed a continuous diffusion of t-AUCB from 2 h after application to beyond 24 h. A single topical administration of a soluble epoxide hydrolase inhibitor improves microcirculatory function in the skin of db/db mice and might represent a new therapeutic approach for preventing the development of skin complications in diabetic patients.

Introduction: Hypothermia and frostbite occur when there is a significant decrease in central and peripheral body temperature in individuals exposed to cold windy conditions, often at high altitude or in a mountain environment. Portable hyperbaric chambers increase the barometric pressure and thereby the partial pressure of oxygen inside the chamber, and their use is a well-known treatment for altitude illness. This study aims to show that a portable hyperbaric chamber could also be used to treat hypothermia and frostbite in the field, when rescue or descent is impossible or delayed., Methods: During a European research program (SOS-MAM, Flow Pulse study) measurements were taken from 27 healthy nonacclimatized voluntary subjects (21 men, 6 women, mean age 41 ± 17) at an altitude of 3800 m (Chamonix Mountain Lab, Aiguille du Midi, France) right before and immediately after spending 1 hour in a portable hyperbaric chamber at 300 mbar. We measured digital cutaneous temperature (Tcut), digital cutaneous blood flow (Fcut), digital tissue oxygenation (T c PO 2 ), blood oxygen saturation (S p O 2 ), heart rate, and core temperature. Air temperature inside the chamber (Tchamb) was measured throughout the whole session., Results: We observed significant increases in Tchamb: 9.3°C compared with the outside temperature, Tcut: +7.5°C (±6.2°C 71%), Fcut: +58 PU (±89) (+379%), T c PO 2 : +18 mmHg (±11.9) (304%), and S p O 2 : 13%., Conclusion: This study shows that a portable hyperbaric chamber can be used to treat frostbite and/or hypothermia in the field at altitude when descent or rescue is impossible or even simply delayed.