Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and anti-opioid by actions on pain modulatory cells within the RVM. One consequence of activation of RVM CCK2 receptors may be enhanced spinal nociceptive transmission but how this might occur, especially in states of pathological pain is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold following ligation of L5/L6 spinal nerves (SNL). Microinjection of CCK into the RVM of naïve rats elicited hypersensitivity to tactile stimulation of the hindpaw. Additionally, RVM CCK elicited a time-related increase in PGE2 measured in cerebrospinal fluid from the lumbar spinal cord. The peak increase in spinal PGE2 was approximately 5-fold and was observed at approximately 80-min post-RVM CCK, a time coincident with maximal RVM CCK-induced mechanical hypersensitivity. Spinal administration of naproxen, a non-selective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-HIAA, a 5-HT metabolite, as compared to controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT3 antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE2 and 5-HT in the spinal cord.

Background: The impact of the 2019 coronavirus pandemic on the mental health of millions worldwide has been well documented, but its impact on prevention and treatment of mental and behavioral health conditions is less clear. The COVID-19 pandemic also created numerous challenges and opportunities to implement health care policies and programs under conditions that are fundamentally different from what has been considered to be usual care. Methods: We conducted a qualitative study to determine the impact of the COVID-19 pandemic on implementation of evidence-based policy and practice by State Mental Health Authorities (SMHA) for prevention and treatment of mental health problems in children and adolescents. Semi-structured interviews were conducted with 29 SMHA representatives of 21 randomly selected states stratified by coronavirus positivity rate and rate of unmet services need. Data analysis with SMHA stakeholders used procedures embedded in the Rapid Assessment Procedure—Informed Community Ethnography methodology. Results: The need for services increased during the pandemic due primarily to family stress and separation from peers. States reporting an increase in demand had high coronavirus positivity and high unmet services need. The greatest impacts were reduced out-of-home services and increased use of telehealth. Barriers to telehealth services included limited access to internet and technology, family preference for face-to-face services, lack of privacy, difficulty using with young children and youth in need of substance use treatment, finding a Health Insurance Portability and Accountability Act (HIPAA)-compliant platform, training providers and clients, and reimbursement challenges. Policy changes to enable reimbursement, internet access, training, and provider licensing resulted in substantially fewer appointment cancellations or no-shows, greater family engagement, reduction in travel time, increased access for people living in remote locations, and increased provider communication and collaboration. States with high rates of coronavirus positivity and high rates of unmet need were most likely to continue use of telehealth post-pandemic. Despite these challenges, states reported successful implementation of policies designed to facilitate virtual services delivery with likely long-term changes in practice. Conclusions: Policy implementation during the pandemic provided important lessons for planning and preparedness for future public health emergencies. Successful policy implementation requires ongoing collaboration among policy makers and with providers.

Suppressor of IKK epsilon ( SIKE ) is associated with the type I interferon response of the innate immune system through TANK ‐binding kinase 1 ( TBK 1). Originally characterized as an endogenous inhibitor of TBK 1 when overexpressed in viral infection and pathological cardiac hypertrophic models, a mechanistic study revealed that SIKE acts as a high‐affinity substrate of TBK 1, but its function remains unknown. In this work, we report that scratch assay analysis of parental and SIKE CRISPR /Cas9 knockout HAP 1 cells showed an ~ 20% decrease in cell migration. Investigation of the SIKE interaction network through affinity purification/mass spectrometry showed that SIKE formed interactions with cytoskeletal proteins. In immunofluorescence assays, endogenous SIKE localized to cytosolic puncta in both epithelial and myeloid cells and to nuclear puncta in myeloid cells, while in epithelial cells additional staining occurred in stress fiber‐like structures and adjacent to the plasma membrane. Using cellular markers, co‐occurrence of SIKE fluorescence with actin, α‐actinin, and ezrin was detected. Reciprocal immunoprecipitation revealed a SIKE :tubulin interaction sensitive to the phosphorylation state of SIKE , but a SIKE :α‐actinin interaction was unchanged by SIKE phosphorylation. In vitro precipitation assays confirmed a direct SIKE interaction with tubulin and α‐actinin. These results indicate that SIKE may promote cell migration by directly associating with the cytoskeleton. In this role, SIKE may mediate cytoskeletal rearrangement necessary in innate immunity, but also link a key catalytic hub, TBK 1, to the cytoskeleton. Database The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD 007262.

Implementation of evidence-based treatments in funded trials is often supported by expert case consultation for clinicians; this may be financially and logistically difficult in clinical practice. Might less costly implementation support produce acceptable treatment fidelity and clinical outcomes? Method: To find out, we trained 42 community clinicians from four community clinics in Modular Approach to Therapy for Children (MATCH), then randomly assigned them to receive multiple lower-cost implementation supports (LC) or expert MATCH consultation plus lower-cost supports (CLC). Clinically referred youths (N ϭ 200; ages 7-15 years, M ϭ 10.73; 53.5% male; 32.5% White, 27.5% Black, 24.0% Latinx, 1.0% Asian, 13.5% multiracial, 1.5% other) were randomly assigned to LC (n ϭ 101) or CLC (n ϭ 99) clinicians, and groups were compared on MATCH adherence and competence, as well as on

Emery-Dreifuss disease is a benign X-linked muscular dystrophy characterized by a distinct pattern of muscle weakness, which is of insidious onset and slow progression. It is associated with atrial paralysis that results in sudden death in early adulthood if left untreated. The authors report the documentation of electrical and mechanical silence confined to the atria in a patient with this disease. Electrocardiography and electrophysiological study document the absence of electrical atrial activity, and inability to pace the atria. Hemodynamic studies demonstrate the absence of A waves, and angiography revealed immobility of the atria. This patient has done well following the institution of permanent ventricular pacing. His brother, who also had muscular dystrophy, died a sudden cardiac death at the age of 29 after refusing medical intervention. Emery-Dreifuss muscular dystrophy is particularly worthy of recognition because of the preventable occurrence of sudden death in young patients with an otherwise excellent prognosis. Permanent ventricular pacing is indicated.