Background: The Ca 2+ /calmodulin-stimulated adenylyl cyclase (AC) isoforms AC1 and AC8, couple NMDA receptor activation to cAMP signaling pathways in neurons and are important for development, learning and memory, drug addiction and persistent pain. AC1 and AC8 in the anterior cingulate cortex (ACC) and the spinal cord were previously shown to be important in subcutaneous inflammatory pain. Muscle pain is different from cutaneous pain in its characteristics as well as conducting fibers. Therefore, we conducted the present work to test the role of AC1 and AC8 in both acute persistent and chronic muscle pain.

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Objective:Our objective was to determine whether altered naive CD4 T-cell biology contributes to development of disease progression in secondary progressive multiple sclerosis (SPMS).Methods:We compared the naive CD4 T-cell gene expression profiles of 19 patients with SPMS and 14 healthy controls (HCs) using a whole-genome microarray approach. We analyzed surface protein expression of critical genes by flow cytometry after T-cell receptor (TCR) stimulation of naive CD4 T cells isolated from HCs and patients with SPMS.Results:Hierarchical clustering segregated patients with SPMS into 2 subgroups: SP-1, which had a short duration of relapsing-remitting multiple sclerosis (MS), and SP-2, which had a long duration of relapsing-remitting MS. SP-1 patients upregulated numerous immune genes, including genes within TCR and toll-like receptor (TLR) signaling pathways. SP-2 patients showed immune gene downregulation in comparison with HCs. We identified an SP-1–specific transcriptional signature of 3 genes (TLR4, TLR2, and chemokine receptor 1), and these genes had higher surface protein expression in SP-1 than in SP-2. After TCR stimulation for 48 hours, only SP-1 showed a progressive linear increase in TLR2 and TLR4 protein expression.Conclusions:Differences in naive CD4 T-cell biology, notably of TCR and TLR signaling pathways, identified patients with MS with more rapid conversion to secondary progression, a critical determinant of long-term disability in MS.

The current coronavirus disease (COVID-19) pandemic has rapidly spread across the world. Individuals with stimulant use disorder are a vulnerable population, who are particularly at risk of negative outcomes during this pandemic due to several risk factors, including mental and physical comorbidities, weakened immune responses, high-risk behaviors, and barriers to healthcare access. Engaging patients with stimulant use disorder in regular treatment has become even more difficult during this pandemic, which has resulted in many cuts to addiction treatment programs. The most effective treatment options for stimulant use disorder are psychosocial interventions, which rely heavily on in-person interactions, posing an added challenge during physical distancing. In particular, contingency management (CM) is a behavioral therapy that utilizes tangible reinforcements to incentivize targeted behavior changes, and is an effective treatment intervention used for stimulant use disorder. This paper highlights the treatment challenges for individuals with stimulant use disorder and the importance of adapting CM programs during COVID-19. We present strategies for how CM can be adapted and its role expanded in a safe way during the COVID-19 pandemic to help prevent infection spread, stimulant use relapse, and worsened psychosocial consequences.

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