Role of the CD39/CD73 Purinergic Pathway in Modulating Arterial Thrombosis in Mice.

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-ß-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.

Mobile app self-care versus in-office care for stress reduction: a cost minimization analysis.

We calculated the cost of providing stress reduction care with a mobile phone app (Breathe2Relax) in comparison with normal in-person care, the standard method for managing stress in military and civilian populations. We conducted a cost-minimization analysis. The total cost to the military healthcare system of treating 1000 patients with the app was $106,397. Treating 1000 patients with in-office care cost $68,820. Treatment using the app became less expensive than in-office treatment at approximately 1600 users. From the perspective of the civilian healthcare system, treatment using the app became less expensive than in-office treatment at approximately 1500 users. An online tool was used to obtain data about the number of app downloads and usage sessions. A total of 47,000 users had accessed the app for 10-30 min sessions in the 2.5 years since the release of the app. Assuming that all 47,000 users were military beneficiaries, the savings to the military healthcare system would be $2.7 million; if the 47,000 users were civilian, the savings to the civilian healthcare system would be $2.9 million. Because of the large number of potential users, the total societal savings resulting from self-care using the app may be considerable.

Soldiers' preferences for follow-up communications with behavioral health providers.

BACKGROUND: Recent research has shown value in utilizing follow-up communication with patients to improve long-term outcomes of behavioral health, particularly among the most high-risk patients. MATERIALS AND METHODS: We surveyed 38 active-duty Army personnel who were attached as behavioral health patients to a Warrior Transition Unit at a large military installation to ask their preferences for follow-up communication to behavioral healthcare. RESULTS: Strongest preferences for contact were (1) personal cellphone, (2) text message, and (3) e-mail to non-work account. Because of frequent endorsement of stigma as a barrier to behavioral health treatment in this population, we also evaluated the influence of stigma on follow-up preferences. CONCLUSIONS: "High-stigma" participants indicated less favor for a personal note from a behavioral healthcare provider following treatment, although both high- and low-stigma participants agreed it was a "good idea" for a provider to e-mail a link to a Web site with relevant information about a diagnosis.

Design and methodology of a randomized clinical trial of home-based telemental health treatment for U.S. military personnel and veterans with depression.

Home-based telemental health (TMH) treatments have the potential to address current and future health needs of military service members, veterans, and their families, especially for those who live in rural or underserved areas. The use of home-based TMH treatments to address the behavioral health care needs of U.S. military healthcare beneficiaries is not presently considered standard of care in the Military Health System. The feasibility, safety, and clinical efficacy of home-based TMH treatments must be established before broad dissemination of home-based treatment programs can be implemented. This paper describes the design, methodology, and protocol of a clinical trial that compares in-office to home-based Behavioral Activation for Depression (BATD) treatment delivered via web-based video technology for service members and veterans with depression. This grant funded three-year randomized clinical trial is being conducted at the National Center for Telehealth and Technology at Joint-base Lewis-McChord and at the Portland VA Medical Center. Best practice recommendations regarding the implementation of in-home telehealth in the military setting as well as the cultural and contextual factors of providing in-home care to active duty and veteran military populations are also discussed.

Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field study.

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, double-blind 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 50 mg of oral DHEA supplementation daily for 5 days during classroom training followed by 7 days of 75 mg 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.

Effect of psychological skills training during military survival school: a randomized, controlled field study.

In this randomized, controlled field study, we examined the effects of a brief psychological skills training (PST) intervention on stress responses during military survival school. A second purpose was to build upon prior research in this unique environment by extending the follow-up window to 3 months. Baseline subjective distress (dissociative) symptoms were measured in 65 male military subjects, who were then randomized either to PST or a control group that received no training beyond the normal survival school curriculum. PST received training in arousal control, mental imagery, goal setting, and positive self-talk in two separate 40-minute sessions before stressful field exercises. Stress symptoms were then assessed during a mock-captivity phase of training, as well as 24 hours, 1 month, and 3 months after completion of training. Repeated-measures analyses of variance with follow-up paired t tests examined differences between groups and across time. Survival training precipitated remarkable increases in subjective distress, but few substantive group differences emerged. This study extends prior work quantifying the human stress response to intense military training.