AAV-mediated expression of PFKFB3 in myofibers, but not endothelial cells, improves ischemic muscle function in mice with critical limb ischemia.

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a powerful driver of angiogenesis through its modulation of glycolytic metabolism within endothelial cells. Recent work has demonstrated that PFKFB3 modulates the response to muscle ischemia, however the cell specificity of these effects is not fully understood. In this study, we tested the impact of viral mediated expression of PFKFB3, driven by gene promoters specific for myofibers or endothelial cells, on ischemic hindlimb revascularization and muscle function.

Measurements of Atmospheric Methane Emissions from Stray Gas Migration: A Case Study from the Marcellus Shale.

Understanding emissions of methane from legacy and ongoing shale gas development requires both regional studies that assess the frequency of emissions and case studies that assess causation. We present the first direct measurements of emissions in a case study of a putatively leaking gas well in the largest shale gas play in the United States. We quantify atmospheric methane emissions in farmland >2 km from the nearest shale gas well cited for casing and cementing issues.

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment.

Dopamine system deficiencies and associated behavioral phenotypes may be a critical barrier to success in treating stimulant use disorders. Similarities in dopamine dysfunction between cocaine and methamphetamine use disorder but also key differences may impact treatment efficacy and outcome. This review will first compare the epidemiology of cocaine and methamphetamine use disorder.

Psychopathy and Corticostriatal Connectivity: The Link to Criminal Behavior in Methamphetamine Dependence.

Methamphetamine use and psychopathy are associated with criminal behavior; however, it is unclear how methamphetamine use and psychopathy interact to promote violent, economic and drug offenses. Abnormalities in corticostriatal functional connectivity are exhibited in both psychopathic and methamphetamine dependent individuals, which may contribute to criminal behavior through maladaptive and impulsive decision-making processes. This study shows that psychopathic traits contribute to weaker corticostriatal connectivity in methamphetamine dependence and contributes to an increase in criminal behavior.

Correction to: Neural correlates of reward magnitude and delay during a probabilistic delay discounting task in alcohol use disorder.

After publication of this paper, the authors determined an error in the funding information section CX17008-CDA2 should be CX001790 (MK).

Neural correlates of reward magnitude and delay during a probabilistic delay discounting task in alcohol use disorder.

Rationale: Alcohol-use disorder (AUD) is associated with the propensity to choose smaller sooner options on the delay discounting task. It is unclear, however, how inherent risk underlies delay discounting behavior. As impulsive choice is a hallmark feature in AUD, it is important to understand the neural response to reward and delay while accounting for risk in impulsive decision-making.

Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics.

Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6/J mice were subjected to a diet-induced model of CKD by delivery of adenine for six weeks.

Effects of Naltrexone on Large-Scale Network Interactions in Methamphetamine Use Disorder.

Naltrexone attenuates craving, and the subjective effects of methamphetamine and extended-release naltrexone (XR-NTX) reduces functional connectivity between regions of the striatum and limbic cortex. Naltrexone modulates neural activity at dopaminergic synapses; however, it is unclear whether naltrexone has an effect on large-scale brain networks. Functional networks interact to coordinate behavior, and as substance-use disorders are associated with an imbalance between reward and cognitive control networks, treatment approaches that target interactive brain systems underlying addiction may be a useful adjunct for behavioral therapies.

Neuroinflammation in addiction: A review of neuroimaging studies and potential immunotherapies.

Addiction is a worldwide public health problem and this article reviews scientific advances in identifying the role of neuroinflammation in the genesis, maintenance, and treatment of substance use disorders. With an emphasis on neuroimaging techniques, this review examines human studies of addiction using positron emission tomography to identify binding of translocator protein (TSPO), which is upregulated in reactive glial cells and activated microglia during pathological states. High TSPO levels have been shown in methamphetamine use but exhibits variable patterns in cocaine use.

A preliminary randomized clinical trial of naltrexone reduces striatal resting state functional connectivity in people with methamphetamine use disorder.

Objective: Naltrexone has been shown to attenuate craving and the subjective effects of methamphetamine. Although naltrexone has modulatory effects on neural activity at dopaminergic synapses, the effect on striatal connectivity is unclear. As methamphetamine use is associated with greater resting-state functional connectivity (RSFC) in the dopaminergic system, we examined whether extended-release naltrexone (XR-NTX) can normalize striatal connectivity and whether changes in RSFC are associated with changes in craving and methamphetamine use.

The relationship between interleukin-6 and functional connectivity in methamphetamine users.

Methamphetamine (MA) causes an increase in pro-inflammatory cytokines in animal models and in humans. Resulting activation of microglia and neuro-inflammation could, via effects on reward networks, mediate behavioral characteristics of addiction. We examined the relationship between interleukin-6 (IL-6) and corticolimbic and striatolimbic resting-state functional connectivity (RSFC).

Healthy Adults Display Long-Term Trait-Like Neurobehavioral Resilience and Vulnerability to Sleep Loss.

Sleep loss produces well-characterized cognitive deficits, although there are large individual differences, with marked vulnerability or resilience among individuals. Such differences are stable with repeated exposures to acute total sleep deprivation (TSD) within a short-time interval (weeks). Whether such stability occurs with chronic sleep restriction (SR) and whether it endures across months to years in TSD, indicating a true trait, remains unknown.

Executive Control and Striatal Resting-State Network Interact with Risk Factors to Influence Treatment Outcomes in Alcohol-Use Disorder.

Alterations within mesocorticolimbic terminal regions commonly occur with alcohol use disorder (AUD). As pathological drug-seeking behavior may arise as a consequence of alcohol-induced neuroadaptations, it is critical to understand how such changes increase the likelihood of relapse. This report examined resting-state functional connectivity (RSFC) using both a seed-based and model-free approach in individuals in treatment for AUD and how dysregulation of network connectivity contributes to treatment outcomes.

Phenotypic Stability of Energy Balance Responses to Experimental Total Sleep Deprivation and Sleep Restriction in Healthy Adults.

Experimental studies have shown that sleep restriction (SR) and total sleep deprivation (TSD) produce increased caloric intake, greater fat consumption, and increased late-night eating. However, whether individuals show similar energy intake responses to both SR and TSD remains unknown. A total of = 66 healthy adults (aged 21-50 years, 48.