Cytomegalovirus US28 regulates cellular EphA2 to maintain viral latency.

Cytomegalovirus (CMV) reactivation from latency following immune dysregulation remains a serious risk for patients, often causing substantial morbidity and mortality. Here, we demonstrate the CMV-encoded G protein-coupled receptor, US28, in coordination with cellular Ephrin receptor A2, attenuates mitogen-activated protein kinase signaling, thereby limiting viral replication in latently infected primary monocytes. Furthermore, treatment of latently infected primary monocytes with dasatinib, a Food and Drug Association-approved kinase inhibitor used to treat a subset of leukemias, results in CMV reactivation. These ex vivo data correlate with our retrospective analyses of the Explorys electronic health record database, where we find dasatinib treatment is associated with a significant risk of CMV-associated disease (odds ratio 1.58, P = 0.0004). Collectively, our findings elucidate a signaling pathway that plays a central role in the balance between CMV latency and reactivation and identifies a common therapeutic cancer treatment that elevates the risk of CMV-associated disease.

Depressive Symptom Trajectories Among People Living with HIV in a Collaborative Care Program.

Depressive symptoms may differ in severity and change over time in people living with HIV (PLWH). Describing depression trajectories and associated clinical characteristics of PLWH in an interventional study may help in developing a more personalized medicine approach. Using latent class growth analysis four, 15-month self-reported depression trajectories were identified in 416 PLWH participating in a collaborative care program. The four subgroups were characterized by improving (58.4% [of participants]), worsening (9.4%), highly responsive (19.5%) and persistently severe (12.7%) depressive symptoms. A high proportion of individuals were in trajectories marked by improvement. Further, the highly responsive group had on average, over 50% reduction of self-reported depressive symptoms. Self-reported trauma, posttraumatic stress disorder, lower neighborhood-level education and fewer HIV and psychiatry clinic visits were associated with worsening or persistently severe depressive symptom trajectories. Members of the persistently severe group were less likely to be virally suppressed after 12-months. Identifying subgroups of PLWH based on changes in self-reported depressive symptoms may further inform intervention approaches that can advance care.

Manual physical therapy and exercise versus supervised home exercise in the management of patients with inversion ankle sprain: a multicenter randomized clinical trial.

STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To compare the effectiveness of manual therapy and exercise (MTEX) to a home exercise program (HEP) in the management of individuals with an inversion ankle sprain. BACKGROUND: An in-clinic exercise program has been found to yield similar outcomes as an HEP for individuals with an inversion ankle sprain. However, no studies have compared an MTEX approach to an HEP. METHODS: Patients with an inversion ankle sprain completed the Foot and Ankle Ability Measure (FAAM) activities of daily living subscale, the FAAM sports subscale, the Lower Extremity Functional Scale, and the numeric pain rating scale. Patients were randomly assigned to either an MTEX or an HEP treatment group. Outcomes were collected at baseline, 4 weeks, and 6 months. The primary aim (effects of treatment on pain and disability) was examined with a mixed-model analysis of variance. The hypothesis of interest was the 2-way interaction (group by time). RESULTS: Seventy-four patients (mean ± SD age, 35.1 ± 11.0 years; 48.6% female) were randomized into the MTEX group (n = 37) or the HEP group (n = 37). The overall group-by-time interaction for the mixed-model analysis of variance was statistically significant for the FAAM activities of daily living subscale (P<.001), FAAM sports subscale (P<.001), Lower Extremity Functional Scale (P<.001), and pain (P ≤.001). Improvements in all functional outcome measures and pain were significantly greater at both the 4-week and 6-month follow-up periods in favor of the MTEX group. CONCLUSION: The results suggest that an MTEX approach is superior to an HEP in the treatment of inversion ankle sprains. Registered at clinicaltrials.gov (NCT00797368). LEVEL OF EVIDENCE: Therapy, level 1b-.