A Review of Murine Cytomegalovirus as a Model for Human Cytomegalovirus Disease-Do Mice Lie?

Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The species-specific nature of HCMV restricts most research to cell culture-based studies or to the investigation of non-invasive clinical samples, which may not be ideal for the study of disseminated disease. Initial MCMV research used a salivary gland-propagated virus administered via different routes of inoculation into a variety of mouse strains. This revealed that the genetic background of the laboratory mice affected the severity of disease and altered the extent of subsequent pathology. The advent of genetically modified mice and viruses has allowed new aspects of disease to be modeled and the opportunistic nature of HCMV infection to be confirmed. This review describes the different ways that MCMV has been used to model HCMV diseases and explores the continuing difficulty faced by researchers attempting to model HCMV congenital cytomegalovirus disease using the mouse model.

Randomized Trial of Therapy Dogs Versus Deliberative Coloring (Art Therapy) to Reduce Stress in Emergency Medicine Providers.

OBJECTIVE: Cognitive stress during shift work contributes to burnout in emergency department (ED) workers. We hypothesize that if physicians and nurses interact with a therapy dog for 5 minutes while on ED shift, both their perceived and their manifested stress levels will decrease. METHODS: In this single-center, prospective, randomized controlled clinical trial (NCT03628820), we tested the effectiveness of therapy dogs versus coloring a mandala and versus no intervention (control) on provider stress. Consenting emergency medicine physicians and nurses provided three self-reported assessments of stress and saliva samples at the start (T1), at the middle (T2), and near the end (T3) of shift. Thirty minutes prior to T2, participants were randomized to either interacting with a therapy dog or coloring for 5 minutes; controls had neither. Stress was assessed on visual analog scale (VAS, 0-100 mm) and with salivary cortisol (Salimetrics) and the modified Perceived Stress Scale (mPSS-10). To assess potential change in participant behavior, patients of providers in either group were asked to complete an internally derived survey of empathic behaviors displayed by providers at T1 and T3. RESULTS: We enrolled 122 providers (n = 39 control, n = 40 coloring, n = 43 dog); 48% were residents, and 60% enrolled on an evening shift. At T1, mean (±SD) VAS score was not different between groups (18.2 [±17.8] mm). At T3, VAS tended to increase with coloring (24.5 mm), remain unchanged in controls (20 mm), and decreased slightly with dogs (13.6 mm, p = 0.018 vs. coloring, Tukey's post hoc). Salivary cortisol levels were consistently highest at the beginning of each providers' shift and were significantly decreased versus control in both the dog and the coloring groups (p < 0.05, Tukey's). We observed no difference between groups for the mPSS-10 nor in patient reported survey of empathic behaviors. CONCLUSION: This randomized controlled clinical trial demonstrates preliminary evidence that a 5-minute therapy dog interaction while on shift can reduce provider stress in ED physicians and nurses.

Controlled clinical trial of canine therapy versus usual care to reduce patient anxiety in the emergency department.

OBJECTIVE: Test if therapy dogs reduce anxiety in emergency department (ED) patients. METHODS: In this controlled clinical trial (NCT03471429), medically stable, adult patients were approached if the physician believed that the patient had "moderate or greater anxiety." Patients were allocated on a 1:1 ratio to either 15 min exposure to a certified therapy dog and handler (dog), or usual care (control). Patient reported anxiety, pain and depression were assessed using a 0-10 scale (10 = worst). Primary outcome was change in anxiety from baseline (T0) to 30 min and 90 min after exposure to dog or control (T1 and T2 respectively); secondary outcomes were pain, depression and frequency of pain medication. RESULTS: Among 93 patients willing to participate in research, 7 had aversions to dogs, leaving 86 (92%) were willing to see a dog six others met exclusion criteria, leaving 40 patients allocated to each group (dog or control). Median and mean baseline anxiety, pain and depression scores were similar between groups. With dog exposure, median anxiety decreased significantly from T0 to T1: 6 (IQR 4-9.75) to T1: 2 (0-6) compared with 6 (4-8) to 6 (2.5-8) in controls (P<0.001, for T1, Mann-Whitney U and unpaired t-test). Dog exposure was associated with significantly lower anxiety at T2 and a significant overall treatment effect on two-way repeated measures ANOVA for anxiety, pain and depression. After exposure, 1/40 in the dog group needed pain medication, versus 7/40 in controls (P = 0.056, Fisher's exact test). CONCLUSIONS: Exposure to therapy dogs plus handlers significantly reduced anxiety in ED patients.