Regulation of alcohol drinking by ventral striatum and extended amygdala circuitry.

Alcohol use disorder is a complex psychiatric disorder that can be modeled in rodents using a number of drinking paradigms. Drinking-in-the-dark (DID) is widely used to model the binge/intoxication stage of addiction, and chronic intermittent ethanol vapor procedures (CIE) are used to induce dependence and model withdrawal/negative affect induced escalation of drinking. We discuss experiments showing the ventral striatum (vStr) and extended amygdala (EA) are engaged in response to ethanol in rodents through c-Fos/Fos immunoreactivity studies.

Identification of functionally important domains of human cytomegalovirus gO that act after trimer binding to receptors.

Human cytomegalovirus (HCMV) entry involves trimer (gH/gL/gO) that interacts with PDGFRα in fibroblasts. Entry into epithelial and endothelial cells requires trimer, which binds unidentified receptors, and pentamer (gH/gL/UL128-131), which binds neuropilin-2. To identify functionally important domains in trimer, we screened an overlapping 20-mer gO peptide library and identified two sets of peptides: 19/20 (a.

Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging in rhesus macaques.

Older individuals are at increased risk of developing severe respiratory infections. However, our understanding of the impact of aging on the respiratory tract remains limited as samples from healthy humans are challenging to obtain and results can be confounded by variables such as smoking and diet. Here, we carry out a comprehensive cross-sectional study (n = 34 adult, n = 49 aged) to define the consequences of aging on the lung using the rhesus macaque model.

Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy.

Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.

Methods: Participants were at least 18 years old and had FSHD1/FSHD2.

The Influence of Diet on Metabolism and Health Across the Lifespan in Nonhuman Primates.

The macro and micronutrient composition and the overall quantity of the diet are important predictors of physical and psychological health and, as a consequence, behavior. Translational preclinical models are critical to identifying the mechanisms underlying these relationships. Nonhuman primate models are particularly instrumental to this line of research as they exhibit considerable genetic, social, and physiological similarities, as well as similarities in their developmental trajectories to humans.

Impact of putamen inhibition by DREADDs on schedule-induced drinking in rhesus monkeys.

The putamen is a nucleus within the sensory-motor striatal network that is involved in automatic, habitual actions. Schedule-induced polydipsia (SIP) is highly automated behavior, reliably occurring under intermediate interval schedules of reinforcement. The effect of putamen inhibition in mediating SIP of water and ethanol (4% w/v) under a Fixed Time 5-min (FT-5 min) schedule for food delivery was tested in 12 rhesus monkeys (6 male, 6 female).

Antihyperglycemic activity of L-norvaline and L-arginine in high-fat diet and streptozotocin-treated male rats.

Background: A decrease in nitric oxide (NO) bioavailability has been shown to cause hyperglycemia, type II diabetes mellitus (DM), and chronic cardio-metabolic complications. In turn, hyperglycemia and hypercholesterolemia are associated with increased oxidative stress that leads to reduced nitric oxide bioavailability through disruption of L-arginine transport into cells, inactivation of nitric oxide synthase, and activation of arginase. Upregulation of arginase has been demonstrated in both diabetic patients and animal models of hyperglycemia and type 2 diabetes.

Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder.

Development of better treatments for alcohol use disorder (AUD) is urgently needed. One promising opportunity for this development is the potential of targeting the oxytocin peptide system. Preclinical studies showed that administration of exogenous oxytocin or, more recently, stimulation of neurons expressing endogenous oxytocin lead to a decreased alcohol consumption across several rodent models.

Effect of ethyl cellulose coating as an evaluation agent against contamination on the bond strength of zirconia restorations: An in vitro study.

Statement Of Problem: During the trial placement of zirconia restorations, contamination of the bonding surface is inevitable. Although cleaning methods for contaminated surfaces have been described, a method of preventing saliva contamination of the bonding surface of zirconia restorations is lacking.

Purpose: The purpose of this in vitro study was to investigate an ethyl cellulose coating as an evaluation agent to mitigate the effects of saliva contamination on the bond strength of zirconia restorations.

Internalized stigma, depressive symptoms, and the modifying role of antiretroviral therapy: A cohort study in rural Uganda.

Depression affects over 40% of people with HIV (PHIV) in low- and middle-income countries, and over half of PHIV report HIV-related internalized stigma. However, few longitudinal studies of PHIV have examined the relationship between HIV-related stigma and depression. Data were analyzed from the 2007-15 Uganda AIDS Rural Treatment Outcomes (UARTO) Study, a cohort of 454 antiretroviral therapy (ART)-naïve PHIV (68% women) starting ART.

Risk factors for postoperative pancreatic fistula in the Era of pasireotide.

Introduction: Postoperative pancreatic fistulas (POPFs) remain common; POPFs frequently require intervention, termed clinically-relevant POPFs (crPOPFs). Pasireotide is increasingly used to prevent POPF, however, risk factors for POPF in this population remain unexplored.

Methods: Patients undergoing pancreatectomy with perioperative pasireotide from 2013 to 2020 were identified from our institutional National Surgical Quality Improvement Project database.

Assessing negative affect in mice during abstinence from alcohol drinking: Limitations and future challenges.

Alcohol use disorder (AUD) is frequently comorbid with mood disorders, and these co-occurring neuropsychiatric disorders contribute to the development and maintenance of alcohol dependence and relapse. In preclinical models, mice chronically exposed to alcohol display anxiety-like and depressive-like behaviors during acute withdrawal and protracted abstinence. However, in total, results from studies using voluntary alcohol-drinking paradigms show variable behavioral outcomes in assays measuring negative affective behaviors.

Codelivery of 1α,25-Dihydroxyvitamin D and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.

Surgical site infections represent a significant clinical problem. Herein, we report a nanofiber dressing for topical codelivery of immunomodulating compounds including 1α,25-dihydroxyvitamin D (1,25(OH)D) and VID400, a inhibitor in a sustained manner, for inducing the expression of the endogenous cathelicidin antimicrobial peptide () gene encoding the hCAP18 protein, which is processed into the LL-37 peptide. Nanofiber wound dressings with coencapsulation of 1,25(OH)D and VID400 were generated by electrospinning.

Time for a paradigm shift: The adolescent brain in addiction treatment.

Objective: One route to improve adolescent addiction treatment outcomes is to use translational approaches to help identify developmental neuroscience mechanisms that undergird active treatment ingredients and advance adolescent behavior change.

Methods: This sample included 163 adolescents (ages 15-19) randomized to motivational interviewing (MI) vs. brief adolescent mindfulness (BAM).

Genetic and Brain Mechanisms of Addictive Behavior and Neuroadaptation.

Genetic differences play a role in the susceptibility to addictive drug use, the probability that the use of these drugs will escalate and result in a drug use disorder, and whether relapse to use will occur during or after treatment [...

Pairing food and drink: A physiological model of blood ethanol levels for a variety of drinking behaviors.

We present a blood ethanol concentration compartment model which utilizes an animal's ethanol intake, food intake, and weight to predict the animal's blood ethanol concentration at any given time. By incorporating the food digestion process into the model we can predict blood ethanol concentration levels over time for a variety of drinking and eating scenarios. The model is calibrated and validated using data from cohorts of male monkeys, and is able to capture blood ethanol concentration kinetics of the monkeys from a variety of drinking behavior classifications.

Patient-reported outcomes in patients with acromegaly treated with pegvisomant in the ACROSTUDY extension: A real-world experience.

Purpose: To report the effects of pegvisomant (PEGV) treatment on patient-reported outcomes in acromegaly patients.

Methods: We conducted an extension study of an open-label, multinational, non-interventional study (ACROSTUDY) evaluating the long-term safety and efficacy of PEGV for acromegaly in routine clinical practice. Enrolled patients were rollover patients from ACROSTUDY, or treatment naïve/semi-naïve (NSN; no PEGV within 6 months of enrollment).