Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1β-evoked signaling in vascular smooth muscle cells and vascular inflammation.

Reversible lysine-63 (K63) polyubiquitination regulates proinflammatory signaling in vascular smooth muscle cells (SMCs) and plays an integral role in atherosclerosis. Ubiquitin-specific peptidase 20 (USP20) reduces NFκB activation triggered by proinflammatory stimuli, and USP20 activity attenuates atherosclerosis in mice. The association of USP20 with its substrates triggers deubiquitinase activity; this association is regulated by phosphorylation of USP20 on Ser334 (mouse) or Ser333 (human).

International Consensus Statement on Obstructive Sleep Apnea.

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA).

Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats.

Drebrin attenuates atherosclerosis by limiting smooth muscle cell transdifferentiation.

Aims: The F-actin-binding protein Drebrin inhibits smooth muscle cell (SMC) migration, proliferation, and pro-inflammatory signalling. Therefore, we tested the hypothesis that Drebrin constrains atherosclerosis.

Methods And Results: SM22-Cre+/Dbnflox/flox/Ldlr-/- (SMC-Dbn-/-/Ldlr-/-) and control mice (SM22-Cre+/Ldlr-/-, Dbnflox/flox/Ldlr-/-, and Ldlr-/-) were fed a western diet for 14-20 weeks.

Treatment of Obstructive Sleep Apnea: Choosing the Best Positive Airway Pressure Device.

Positive airway pressure (PAP) remains primary therapy for most patients with obstructive sleep apnea (OSA). CPAP, APAP, and BPAP are all reasonable therapies that can be used for patients with uncomplicated OSA across the spectrum of disease severity. BPAP should be considered for patients who are nonadherent to CPAP or APAP therapy because of pressure intolerance.

Study design considerations for sleep-disordered breathing devices.

In recent years, sleep-disordered breathing (SDB) has been recognized as a prevalent but under-diagnosed condition in adults and has prompted the need for new and better diagnostic and therapeutic options. To facilitate the development and availability of innovative, safe and effective SDB medical device technologies for patients in the United States, the US Food and Drug Administration collaborated with six SDB-related professional societies and a consumer advocacy organization to convene a public workshop focused on clinical investigations of SDB devices. Sleep medicine experts discussed appropriate definitions of terms used in the diagnosis and treatment of SDB, the use of home sleep testing versus polysomnography, clinical trial design issues in studying SDB devices, and current and future trends in digital health technologies for diagnosis and monitoring SDB.

Reducing COPD Readmissions: Strategies for the Pulmonologist to Improve Outcomes.

Hospitalizations for patients with acute exacerbations of COPD are associated with several adverse patient outcomes as well as with significant health-care costs. Despite many interventions targeted at reducing readmissions following an initial hospitalization, there are few strategies that have been consistently associated with reductions in this outcome. Despite the lack of consensus as to the best strategies to deploy to reduce readmissions related to acute exacerbations of COPD, efforts must continue to focus on determining the best approaches for this population.

A Sleep Medicine Curriculum for Pulmonary and Pulmonary/Critical Care Fellowship Programs: A Multisociety Expert Panel Report.

Background: Pulmonary medicine specialists find themselves responsible for the diagnosis and management of patients with sleep disorders. Despite the increasing prevalence of many of these conditions, many sleep medicine fellowship training slots go unfilled, leading to a growing gap between the volume of patients seeking care for sleep abnormalities and the number of physicians formally trained to manage them. To address this need, we convened a multisociety panel to develop a list of curricular recommendations related to sleep medicine for pulmonary fellowship training programs.

USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.

Objective- Signaling that activates NFκB (nuclear factor κB) in smooth muscle cells (SMCs) is integral to atherosclerosis and involves reversible ubiquitination that activates proteins downstream of proatherogenic receptors. Deubiquitination of these proteins is mediated by USP20 (ubiquitin-specific protease 20), among other deubiquitinases. We sought to determine whether USP20 activity in SMCs decreases atherosclerosis.

Doing It Better for Less: Incorporating OSA Management Into Alternative Payment Models.

As the cost of health care continues to escalate, payers are adapting by moving away from models based on traditional fee-for-service reimbursement to models focused on rewarding care delivery that reduces costs and improves quality. These alternative payment models (APMs) are being introduced by government and commercial payers and will likely become the norm over time. Recent changes in sleep medicine related to advances in technology and approaches by payers for the management of OSA make this an appropriate time to incorporate the delivery of sleep medicine services into APMs.

Drebrin regulates angiotensin II-induced aortic remodelling.

Aims: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebrin inhibits angiotensin II-induced remodelling of the proximal aorta.

Methods And Results: Angiotensin II was administered via osmotic minipumps at 1000 ng/kg/min continuously for 28 days in SM22-Cre+/Dbnflox/flox (SMC-Dbn-/-) and control mice.

Treatment of Obstructive Sleep Apnea: Choosing the Best Positive Airway Pressure Device.

Positive airway pressure (PAP) remains primary therapy for most patients with obstructive sleep apnea (OSA). CPAP, APAP, and BPAP are all reasonable therapies that can be used for patients with uncomplicated OSA across the spectrum of disease severity. BPAP should be considered for patients who are nonadherent to CPAP or APAP therapy because of pressure intolerance.

Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells.

Aims: Chronic kidney disease (CKD) is a powerful independent risk factor for cardiovascular events, including vein graft failure. Because CKD impairs the clearance of small proteins, we tested the hypothesis that CKD exacerbates vein graft disease by elevating serum levels of critical cytokines that promote vein graft neointimal hyperplasia.

Methods And Results: We modelled CKD in C57BL/6 mice with 5/6ths nephrectomy, which reduced glomerular filtration rate by 60%, and we modelled vein grafting with inferior-vena-cava-to-carotid interposition grafting.

C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways.

Biased agonism, the ability of different ligands for the same receptor to selectively activate some signaling pathways while blocking others, is now an established paradigm for G protein-coupled receptor signaling. One group of receptors in which endogenous bias is critical is the chemokine system, consisting of over 50 ligands and 20 receptors that bind one another with significant promiscuity. We have previously demonstrated that ligands for the same receptor can cause biased signaling responses.

Regulation of inflammation by β-arrestins: Not just receptor tales.

The ubiquitously expressed, multifunctional scaffolding proteins β-arrestin1 and β-arrestin2 each affect inflammatory signaling in a variety of cell lines. In addition to binding the carboxyl-terminal tails of innumerable 7-transmembrane receptors, β-arrestins scaffold untold numbers of other plasma membrane and cytoplasmic proteins. Consequently, the effects of β-arrestins on inflammatory signaling are diverse, and context-specific.

The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.

Objective: Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfamily C TRP (TRPC) channels requires the scaffolding protein Homer 1, which associates with the actin-binding protein Drebrin. We found that SMC Drebrin expression is upregulated in atherosclerosis and in response to injury and investigated whether Drebrin inhibits SMC activation, either through regulation of TRP channel function via Homer or through a direct effect on the actin cytoskeleton.

Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation.

Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFκB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity can be impeded by deubiquitinating enzymes like ubiquitin-specific protease 20 (USP20), which can reverse TRAF6 autoubiquitination, and by association with the multifunctional adaptor protein β-arrestin2.

Evolution in reimbursement for sleep studies and sleep centers.

Because of the rapid increase in the volume and costs of polysomnography and other sleep medicine diagnostic services, the Centers for Medicare & Medicaid Services (CMS) recently commissioned the Office of Inspector General (OIG) to review claims submitted for these services. The OIG found numerous cases of inappropriate payment for submitted claims and recommended significant changes in the CMS auditing process for polysomnography claims review. Additionally, a local Medicare Administrative Contractor released the most specific rules and regulations to date regarding billing and payment for sleep medicine services.

Improvements in current treatments and emerging therapies for adult obstructive sleep apnea.

Obstructive sleep apnea (OSA) is common and is associated with a number of adverse outcomes, including an increased risk for cardiovascular disease. Typical treatment approaches, including positive airway pressure, oral appliances, various upper airway surgeries, and/or weight loss, can improve symptoms and reduce the severity of disease in select patient groups. However, these approaches have several potential limitations, including suboptimal adherence, lack of suitability for all patient groups, and/or absence of adequate outcomes data.