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Objective-Circulating blood cells and endothelial cells express ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73). CD39 hydrolyzes extracellular ATP or ADP to AMP. CD73 hydrolyzes AMP to adenosine. The goal of this study was to examine the interplay between CD39 and CD73 cascade in arterial thrombosis. Approach and Results-To determine how CD73 activity influences in vivo thrombosis, the time to ferric chloride-induced arterial thrombosis was measured in CD73-null mice. In response to 5% FeCl3, but not to 10% FeCl3, there was a significant decrease in the time to thrombosis in CD73-null mice compared with wild-Type mice. In mice overexpressing CD39, ablation of CD73 did not inhibit the prolongation in the time to thrombosis conveyed by CD39 overexpression. However, the CD73 inhibitor α-β-methylene-ADP nullified the prolongation in the time to thrombosis in human CD39 transgenic (hC39-Tg)/CD73-null mice. To determine whether hematopoietic-derived cells or endothelial cell CD39 activity regulates in vivo arterial thrombus, bone marrow transplant studies were conducted. FeCl3-induced arterial thrombosis in chimeric mice revealed a significant prolongation in the time to thrombosis in hCD39-Tg reconstituted wild-Type mice, but not on wild-Type reconstituted hCD39-Tg mice. Monocyte depletion with clodronate-loaded liposomes normalized the time to thrombosis in hCD39-Tg mice compared with hCD39-Tg mice treated with control liposomes, demonstrating that increased CD39 expression on monocytes protects against thrombosis. Conclusions-These data demonstrate that ablation of CD73 minimally effects in vivo thrombosis, but increased CD39 expression on hematopoietic-derived cells, especially monocytes, attenuates in vivo arterial thrombosis.

In-home tele-behavioral health treatments have the potential to address current health needs of Service Members, Veterans, and their families, especially for those that live in rural and underserved areas. The use of in-home, web-based treatment to address the psychological needs of Service Members and Veterans is not yet considered standard of care for the DoD. The safety and clinical efficacy of such treatments must be established before broad dissemination of these treatment programs occurs. This study is a two-group (web-based in-home BA vs. in-person BA) prospective randomized controlled trial. Both groups will be assessed at baseline, mid-treatment (Week 4), post-treatment (Week 8), and at a 3-month follow-up visit. The primary outcome variables are safety and hopelessness. Secondary outcome variables include depression, anxiety, PTSD symptoms, attitudes toward seeking mental health services, quality of life, and health care utilization, as well as treatment satisfaction, adherence, and compliance. A total of 120 participants will be recruited with an anticipated completion rate of 108 participants (54 per treatment group). Participants are Regular Service Members, National Guard Members, Reservists, and Veterans recruited at Madigan Army Medical Center and the Portland VA Medical Center.

Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are anabolic prehormones involved in the synthesis of testosterone. Both have been shown to exert neuroprotective effects during stress. In this randomized, controlled, doubleblind field study, we examined the effects of a 12-day DHEA regimen on stress indices in military men undergoing survival training. Forty-eight men were randomized to either a DHEA treatment group or placebo control group. The treatment group received 50mg of oral DHEA supplementation daily for 5 days during classroom training followed by 7 days of 75mg during stressful field operations. Control subjects received identical placebo pills. Salivary assays (DHEA[S], testosterone, and cortisol) were conducted at four time points: distal pre-stress (T1), proximal pre-stress (T2), mock-captivity stress (T3), and 24 h recovery (T4). Subjective distress was also assessed at T1, T3, and T4. As expected, DHEA treatment resulted in higher salivary concentrations of DHEA and DHEAS during daily living, mock-captivity stress, and recovery. Similar patterns were observed for salivary markers of anabolic balance: DHEA/cortisol, DHEAS/cortisol, and testosterone/cortisol concentration ratios. Despite notable time effects, no group differences emerged for subjective distress. A brief, low dose DHEA regimen yielded large increases in salivary DHEA(S) concentrations and enhanced anabolic balance throughout sustained military stress. These physiological changes did not extrapolate to subjective distress., Published in Stress, 2011. Prepared in collaboration with the Stress Physiology Research Core, Department 162 (Warfighter Performance), Naval Health Research Center, San Diego, CA,. Prepared in cooperation with the Center for Security Forces, Detachment North Island, San Diego, CA. Sponsored in part by the Office of Naval Research Force Health Protection Program.