SPTLC3 Is Essential for Complex I Activity and Contributes to Ischemic Cardiomyopathy.

Background: Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, and cellular roles are not completely understood. Sphingolipids are produced by the serine palmitoyltransferase enzyme, canonically composed of 2 subunits, SPTLC1 (serine palmitoyltransferase long chain base subunit 1) and SPTLC2 (serine palmitoyltransferase long chain base subunit 2). Noncanonical sphingolipids are produced by a more recently described subunit, SPTLC3 (serine palmitoyltransferase long chain base subunit 3).

Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review.

In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as "first-in-class" (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development.

Relationship between baseline plasma p-tau181 and longitudinal changes in cognition and structural brain measures in a cohort of cognitively unimpaired older adults.

Introduction: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy.

Methods: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults.

Complementary and integrative interventions for PTSD.

To treat the impact of trauma, most current evidence supports the use of trauma-focused psychotherapy as the first line approach. However, millions of individuals exposed to trauma worldwide seek Complementary and Integrative Health (CIH) therapies in hopes of achieving wellness above and beyond reducing symptoms. But what is the evidence for CIH interventions? What are potential pitfalls? Given the growing popularity of and strong interest in CIH, EJPT is featuring research on these approaches in this special issue.

Development of a Novel Score to Predict Urgent Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention.

Estimating the likelihood of urgent mechanical circulatory support (MCS) can facilitate procedural planning and clinical decision-making in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We analyzed 2,784 CTO PCIs performed between 2012 and 2021 at 12 centers. The variable importance was estimated by a bootstrap applying a random forest algorithm to a propensity-matched sample (a ratio of 1:5 matching cases with controls on center).

Feasibility and initial impact of single-session internet-delivered acceptance change skills for emotions for stress- and trauma-related problems: a randomized controlled trial.

Background: Current psychological trauma-focused interventions have left a gap for individuals who may not be ready for trauma-focused treatment and/or who present with other forms of clinically significant distress, such as subthreshold post-traumatic stress disorder (PTSD). Emotion regulation is a possible transdiagnostic mechanism of change that may promote and maintain some of the varied mental health problems related to trauma exposure.

Aims: This study examines the feasibility and initial impact of two brief emotion regulation skill trainings targeting different processes hypothesized to reduce trauma-related problems, compared with an active control.

Use of Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention.

The use of mechanical circulatory support (MCS) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We analyzed the clinical and angiographic characteristics, and procedural outcomes of 7,171 CTO PCIs performed between 2012 and 2021 at 35 international centers. Mean age was 64.

Targeting CD38 to Suppress Osteoarthritis Development and Associated Pain After Joint Injury in Mice.

Objective: This study was undertaken to determine the role of CD38, which can function as an enzyme to degrade NAD , in osteoarthritis (OA) development.

Methods: Human knee cartilage from normal donors and OA donors were examined for CD38 expression. "Gain-of-function," through overexpression of CD38 via transient transfection, and "loss-of-function," through pharmacologic inhibition of CD38, approaches were used to assess the effects of CD38 on intracellular NAD :NADH ratio and catabolic activity in chondrocytes.

Proton-Pump Inhibitors and Risk of Calcium Pyrophosphate Deposition in a Population-Based Study.

Objective: There are no proven effective medical treatments to prevent calcium pyrophosphate crystal deposition (CPPD). Hypomagnesemia is a known CPPD risk factor. The present study was undertaken to carry out a real-world epidemiologic study on proton-pump inhibitor (PPI) use, which can cause hypomagnesemia, and CPPD risk.

Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes.

Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1). Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic β-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1.

It Happened Matters More Than What Happened: Associations Between Intimate Partner Violence Abuse Type, Emotion Regulation, and Post-Traumatic Stress Symptoms.

Intimate partner violence (IPV) has varied consequences including post-traumatic stress (PTS). One proposed risk factor for PTS is escalating types of violence; however, data are mixed. Because emotion dysregulation acts as a causal mechanism across numerous problems co-occurring in survivors of IPV, this study examined its association with PTS severity versus abuse type.

Equipment utilization in chronic total occlusion percutaneous coronary interventions: Insights from the PROGRESS-CTO registry.

Background: We examined guidewire and microcatheter utilization during chronic total occlusion (CTO) percutaneous coronary intervention (PCI).

Methods: We examined device utilization in 2,968 CTO PCIs performed in 2,936 patients at 19 US and two international center between January 2016 and January 2019.

Results: The median number of antegrade guidewires used per case declined (5 in 2016 vs 3 in 2019) and was higher in higher complexity lesions (2 in J-CTO 0 vs.

The Impact of Peripheral Artery Disease in Chronic Total Occlusion Percutaneous Coronary Intervention (Insights From PROGRESS-CTO Registry).

The impact of peripheral artery disease (PAD) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We reviewed 3999 CTO PCIs performed in 3914 patients between 2012 and 2018 at 25 centers, 14% of whom had a history of PAD. We compared the clinical and angiographic characteristics and procedural outcomes of patients with versus without history of PAD.

Outcomes of subintimal plaque modification in chronic total occlusion percutaneous coronary intervention.

Background: When crossing into the distal true lumen fails during chronic total occlusion (CTO) percutaneous coronary intervention (PCI), subintimal plaque modification (SPM) is often performed to restore antegrade flow and facilitate subsequent lesion recanalization.

Methods: Between January 2012 and May 4, 2019, 4,659 CTO PCIs were included in the PROGRESS-CTO registry, of which 935 (20%) had a prior unsuccessful attempt. Of those 935 patients, 119 (13%) had prior SPM.

Impact of concomitant treatment of non-chronic total occlusion lesions at the time of chronic total occlusion intervention.

Background: During chronic total occlusion (CTO) percutaneous coronary intervention (PCI), sometimes non-CTO lesions are also treated.

Methods: We compared the clinical and procedural characteristics and outcomes of CTO PCIs with and without concomitant treatment of a non-CTO lesion in a contemporary multicenter CTO registry.

Results: Of the 3598 CTO PCIs performed at 21 centers between 2012 and 2018, 814 (23%) also included PCI of at least one non-CTO lesion.

In-Hospital Outcomes of Chronic Total Occlusion Percutaneous Coronary Interventions in Patients With Prior Coronary Artery Bypass Graft Surgery.

Background: We examined the procedural outcomes of chronic total occlusions (CTO) percutaneous coronary interventions in patients with prior coronary artery bypass graft surgery (CABG).

Methods And Results: We compared the clinical, angiographic characteristics and outcomes of 3486 CTO interventions performed in patients with (n=1101) and without (n=2317) prior CABG at 21 centers. Prior CABG patients (32% of total cohort) were older (67±9 versus 63±10 years; P<0.

Usefulness of Atherectomy in Chronic Total Occlusion Interventions (from the PROGRESS-CTO Registry).

There is limited data on the use of atherectomy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared the clinical and procedural characteristics and outcomes of CTO PCIs performed with or without atherectomy in a contemporary multicenter CTO PCI registry. Between 2012 and 2018, 3,607 CTO PCIs were performed at 21 participating centers.

Regulation of the -Adrenergic Receptor Signaling Pathway in Sustained Ligand-Activated Preconditioning.

Sustained ligand-activated preconditioning (SLP), induced with chronic opioid receptor (OR) agonism, enhances tolerance to ischemia/reperfusion injury in young and aged hearts. Underlying mechanisms remain ill-defined, although early data implicate phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) during the induction phase, and -adrenoceptor ( -AR), G alpha subunit (G ), and protein kinase A (PKA) involvement in subsequent cardioprotection. Here, we tested for induction of a protective -AR/G /PKA signaling axis with SLP to ascertain whether signaling changes were PI3K-dependent (by sustained cotreatment with wortmannin), and whether the downstream PKA target Rho kinase (ROCK) participates in subsequent cardioprotection (by acute treatment with fasudil).