Prescribing Stimulants for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder and Co-occurring Cannabis Use: Considerations for Managing a Clinical Dilemma.

Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in the pediatric population, with 11% of children and adolescents having ever been diagnosed with the disorder. The management of ADHD in the setting of co-occurring cannabis use, which is more prevalent in adolescents with ADHD than in the general population, is an increasingly common dilemma facing clinicians, in part due to recent changes in social acceptability, access, usage, and state-level legal status of cannabis. Clinicians face several considerations, including the following: the confounding effects of cannabis use on assessment and management of ADHD symptoms; the potential reduction in risk of substance use when ADHD symptoms are well managed; and the increased risk of misuse and diversion of stimulants in patients with ongoing cannabis use.

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study.

Patients with autism spectrum disorder (ASD) are at high risk for comorbid major depressive disorder (MDD), which can severely impair functioning and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique, which is Food and Drug Administration (FDA) cleared for the treatment of MDD in adults. Despite demonstrated efficacy in the treatment of depression, there are limited data on the use of rTMS in patients with ASD and comorbid MDD.

SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes.

Steatohepatitis occurs in up to 20% of patients with fatty liver disease and leads to its primary disease outcomes, including fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Mechanisms that mediate this inflammation are of major interest. We previously showed that overload of saturated fatty acids, such as that which occurs with metabolic syndrome, induced sphingosine kinase 1 (SphK1), an enzyme that generates sphingosine-1-phosphate (S1P).

Control of Plasma Membrane Permeability by ABC Transporters.

ATP-binding cassette transporters Pdr5 and Yor1 from Saccharomyces cerevisiae control the asymmetric distribution of phospholipids across the plasma membrane as well as serving as ATP-dependent drug efflux pumps. Mutant strains lacking these transporter proteins were found to exhibit very different resistance phenotypes to two inhibitors of sphingolipid biosynthesis that act either late (aureobasidin A [AbA]) or early (myriocin [Myr]) in the pathway leading to production of these important plasma membrane lipids. These pdr5Δ yor1 strains were highly AbA resistant but extremely sensitive to Myr.

Sphingolipid regulators of cellular dysfunction in Type 2 diabetes mellitus: a systems overview.

Climbing obesity rates have contributed to worldwide increases in obesity-associated diseases, including the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Sphingolipids, an important class of structural and signaling lipids, have emerged as key players in the development and pathogenesis of insulin resistance and T2DM. More specifically, sphingolipids have been demonstrated to play integral roles in lipotoxicity and other aspects of pathogenesis in T2DM, although the cellular mechanisms by which this occurs and by which sphingolipid metabolism is dysregulated in T2DM remain under investigation.

Acid sphingomyelinase plays a key role in palmitic acid-amplified inflammatory signaling triggered by lipopolysaccharide at low concentrations in macrophages.

Periodontal disease is more prevalent and severe in patients with diabetes than in nondiabetic patients. In addition to diabetes, a large number of studies have demonstrated an association between obesity and chronic periodontal disease. However, the underlying mechanisms have not been well understood.

The yeast oxysterol binding protein Kes1 maintains sphingolipid levels.

The oxysterol binding protein family are amphitropic proteins that bind oxysterols, sterols, and possibly phosphoinositides, in a conserved binding pocket. The Saccharomyces cerevisiae oxysterol binding protein family member Kes1 (also known as Osh4) also binds phosphoinositides on a distinct surface of the protein from the conserved binding pocket. In this study, we determine that the oxysterol binding protein family member Kes1 is required to maintain the ratio of complex sphingolipids and levels of ceramide, sphingosine-phosphate and sphingosine.

Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid pool with distinct synthetic routes and functional properties.

Background: Myristate is a novel potential substrate for sphingoid base synthesis.

Results: Myocardial sphingoid base synthesis utilizes myristate; these sphingolipids are functionally non-redundant with canonical sphingoid bases.

Conclusion: d16:0 and d16:1 sphingolipids constitute an appreciable proportion of cardiac dihydrosphingosine and dihydroceramide, with distinct biological roles.

Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes.

Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species.