The skin is the largest organ of the human body and the one mostly exposed to outdoor contaminants. To evaluate the biological mechanisms underlying skin damage caused by fine particulate matter (PM2.5), we analyzed the effects of PM2.5 on cultured human keratinocytes and the skin of experimental animals. PM2.5 was applied to human HaCaT keratinocytes at 50 µg/mL for 24 h and to mouse skin at 100 µg/mL for 7 days. The results indicate that PM2.5 induced oxidative stress by generating reactive oxygen species both in vitro and in vivo, which led to DNA damage, lipid peroxidation, and protein carbonylation. As a result, PM2.5 induced endoplasmic reticulum stress, mitochondrial swelling, and autophagy, and caused apoptosis in HaCaT cells and mouse skin tissue. The PM2.5-induced cell damage was attenuated by antioxidant N-acetyl cysteine, confirming that PM2.5 cellular toxicity was due to oxidative stress. These findings contribute to understanding of the pathophysiological mechanisms triggered in the skin by PM2.5, among which oxidative stress may play a major role.

Background Dysfunction of liver sinusoidal endothelial cells (LSECs) is permissive for the progression of liver fibrosis and cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal vs cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using scRNA-seq technology. Approach & Results Cirrhosis was generated in endothelial specific green fluorescent protein (GFP) reporter mice through carbon tetrachloride inhalation for 12 weeks. GFP-positive liver EC populations were isolated from control and cirrhotic mice by FACS. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. Based on previously reported LSEC-landmarks, we mapped the 3 clusters of LSECs in zones 1, 2, and 3, and determined phenotypic changes in each zone between control and cirrhotic mice. We found genes representing capillarization of LSECs (eg, CD34) as well as extracellular matrix genes were most upregulated in LSECs of zone 3 in cirrhotic mice, which may contribute to the development of basement membranes. LSECs in cirrhotic mice also demonstrated decreased expression of endocytic receptors, most remarkably in zone 3. Transcription factors (Klf2 [Kruppel-like factor-2], Klf4 [Kruppel-like factor-4], and AP-1) that induce nitric oxide production in response to shear stress were downregulated in LSECs of all zones in cirrhotic mice, implying increased intrahepatic vascular resistance. Conclusion This study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most dysfunctional liver ECs.

Enhanced meningeal lymphatic drainage ameliorates neuroinflammation and hepatic encephalopathy in cirrhotic rats Short title: Meningeal lymphatics and hepatic encephalopathy

The combination of transcricothyroid membrane ultrasonography and ultrasonographic lung-sliding evaluation could be useful in confirming endotracheal intubation in the ED.

ObjectivesAlthough ambulance-based telemedicine has been reported to be safe and feasible, its clinical usefulness has not been well documented, and different prehospital management systems would yield different results. The authors evaluated the feasibility and usefulness of telemedicine-assisted direct medical control in the Korean emergency medical service system.MethodsTwenty ambulances in the Busan area were equipped with a telemedicine system. Three-lead electrocardiogram, blood pressure, and pulse oximetry data from the patient and audiovisual input from the scene were transferred to a server. Consulting physicians used desktop computers and the internet to connect to the server. Both requesting emergency medical service (EMS) providers and consulting physicians were asked to fill out report forms and submit them for analysis.ResultsIn the 41 cases in which telemedicine equipment was used, cellular phones were concomitantly used in 28 cases (68.35%) to compensate for the poor audio quality provided by the equipment. The EMS providers rated the video transmission quality with a 4-point average score (interquartile range [IQR] 2-5) on a 5-point scale, and they rated the biosignal transmission quality as 4 (IQR 3-5). The consulting physicians rated the video quality as 4 (IQR 2.5-4) and the biosignal quality as 4 (IQR 3-4). The physicians' ratings for usefulness for making diagnosis or treatment decisions did not differ significantly in relation to the method of communication used.ConclusionsOur study did not find any significant advantage of implementing telemedicine over the use of voice calls in delivering on-line medical control. More user-friendly, smaller devices with clear advantages over voice communication would be required before telemedicine can be successfully implemented in prehospital patient care.