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High intensity exercise is associated with several potentially thrombogenic risk factors, including dehydration and hemoconcentration, vascular trauma, musculoskeletal injuries, inflammation, long-distance travel, and contraceptive usage. These are well documented in case reports of venous thrombosis in track and field athletes. For mountaineers and those working at high altitude, additional risks exist. However, despite there being a high degree of vigilance for "classic" conditions encountered at altitude (eg, acute mountain sickness, high altitude pulmonary edema, and high altitude cerebral edema), mainstream awareness regarding thrombotic conditions and their complications in mountain athletes is relatively low. This is significant because thromboembolic events (including deep vein thrombosis, pulmonary embolism, and cerebral vascular thrombosis) are not uncommon at altitude. We describe a case of deep vein thrombosis and pulmonary embolism in a male mountain guide and discuss the diagnostic issues encountered by his medical practitioners. Potential risk factors affecting blood circulation (eg, seated car travel and compression of popliteal vein) and blood hypercoagulability (eg, hypoxia, environmental and psychological stressors [avalanche risk, extreme cold]) relevant to the subject of this report and mountain athletes in general are identified. Considerations for mitigating and managing thrombosis in addition to personalized care planning at altitude are discussed. The prevalence of thrombosis in mountain athletes is uncharted, but lowlanders increasingly go to high altitude to trek, ski, or climb. Blood clots can and do occur in physically active people, and thrombosis prevention and recognition will demand heightened awareness among participants, healthcare practitioners, and the altitude sport/leisure industry at large., (Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

The protein kinase PKR (protein kinase R) is a sensor in innate immunity. PKR autophosphorylates in the presence of double-stranded RNA enabling it to phosphorylate its substrate, eIF2α (eukaryotic initiation factor 2α), halting cellular translation. Classical activators of PKR are long viral double-stranded RNAs, but recently, PKR has been found to be activated by bacterial RNA. However, the features of bacterial RNA that activate PKR are unknown. We studied the Bacillus subtilis trp 5'-UTR (untranslated region), which is an indirect riboswitch with secondary and tertiary RNA structures that regulate gene function. Additionally, the trp 5'-UTR binds a protein, TRAP (tryptophan RNA-binding attenuation protein), which recognizes l-tryptophan. We present the first evidence that multiple structural features in this RNA, which are typical of bacterial RNAs, activate PKR in TRAP-free and TRAP/l-Trp-bound forms. Segments from the 5'-UTR, including the terminator 5'-stem-loop and Shine-Dalgarno blocking hairpins, demonstrated 5'-triphosphate and flanking RNA tail dependence on PKR activation. Disruption of long-distance tertiary interactions in the 5'-UTR led to partial loss in activation, consistent with highly base-paired regions in bacterial RNA activating PKR. One physiological change a bacterial RNA would face in a human cell is a decrease in the concentration of free magnesium. Upon lowering the magnesium concentration to human physiological conditions of 0.5mM, the trp 5'-UTR continued to activate PKR potently. Moreover, total RNA from Escherichia coli, depleted of rRNA, also activated PKR under these ionic conditions. This study demonstrates that PKR can signal the presence of bacterial RNAs under physiological ionic conditions and offers a potential explanation for the apparent absence of riboswitches in the human genome., (Copyright © 2015 Elsevier Ltd. All rights reserved.)