Vesicular glutamate transporter 2-containing neurons of the centrally-projecting Edinger-Westphal nucleus regulate alcohol drinking and body temperature.

Previous studies in rodents have repeatedly demonstrated that the centrally-projecting Edinger-Westphal nucleus (EWcp) is highly sensitive to alcohol and is also involved in regulating alcohol intake and body temperature. Historically, the EWcp has been known as the main site of Urocortin 1 (Ucn1) expression, a corticotropin-releasing factor-related peptide, in the brain. However, the EWcp also contains other populations of neurons, including neurons that express the vesicular glutamate transporter 2 (Vglut2).

Combined and sequential effects of alcohol and methamphetamine in animal models.

Comorbid drug use, often alcohol with other drugs, poses significant health and societal concerns. Methamphetamine is among the illicit drugs most often co-used with alcohol. The current review examines the animal literature for impacts of comorbid alcohol and methamphetamine exposure.

Confirmation of a Causal Allelic Variant in Addiction-Relevant Methamphetamine Behaviors.

Sensitivity to rewarding and reinforcing drug effects has a critical role in initial use, but the role of initial aversive drug effects has received less attention. Methamphetamine effects on dopamine re-uptake and efflux are associated with its addiction potential. However, methamphetamine also serves as a substrate for the trace amine-associated receptor 1 (TAAR1).

Replicability in measures of attentional set-shifting task performance predicting chronic heavy drinking in rhesus monkeys.

This study was designed to replicate and extend a previous report that the increase in performance of an attentional set-shifting task (ASST) in rhesus monkeys predicted their future alcohol drinking status as a heavy drinker (HD) or non-heavy drinker (NHD). A cohort of 6 young adult male monkeys was trained and tested under the same ASST and then underwent a alcohol self-administration protocol that maintained open-access (22 hours/day) choice of alcohol or water 7 days/week for approximately 6 months. The average improvement in performance in the ASST, as measured by a performance index, was replicated in the cohort of 6 monkeys when compared to the increase in the task performance in a previous cohort of 9 male monkeys.

Monitoring the cellular metabolism of a membrane-permeant photo-caged phosphatidylinositol 3,4,5-trisphosphate derivative.

To deliver charged lipid derivatives to the cell interior, bioactivatable and photo-activatable protecting groups are frequently used. The intracellular metabolism of the protecting groups, as well as the lipid itself, are key factors that determine biological activity. Here we followed the cellular metabolism of cell-permeant photo-activatable ("caged") and non-caged membrane-permeant analogs of dioctanoyl phosphatidylinositol 3,4,5-trisphosphate (diCPIP) carrying biodegradable protecting groups by mass spectrometry.

Twelve-Month Retention in Opioid Agonist Treatment for Opioid Use Disorder Among Patients With and Without HIV.

Although opioid agonist therapy (OAT) is associated with positive health outcomes, including improved HIV management, long-term retention in OAT remains low among patients with opioid use disorder (OUD). Using data from the Veterans Aging Cohort Study (VACS), we identify variables independently associated with OAT retention overall and by HIV status. Among 7,334 patients with OUD, 13.

Ventral striatal resting-state functional connectivity in adolescents is associated with earlier onset of binge drinking.

Background: Earlier engagement in heavy drinking during adolescence is a risk factor for the development of alcohol use disorders later in life. Longitudinal studies in adolescents have linked brain structure and task-evoked function to future alcohol use; however, less is known about how intrinsic network-level interactions relate to future substance use during this developmental period.

Methods: In this prospective longitudinal study, resting-state functional connectivity of the ventral striatum, risky decision making, and sensation seeking were measured in 73 adolescents at baseline.

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

Background: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12.

Polygenic Breast Cancer Risk for Women Veterans in the Million Veteran Program.

Unlabelled: Accurate breast cancer (BC) risk assessment allows personalized screening and prevention. Prospective validation of prediction models is required before clinical application. Here, we evaluate clinical- and genetic-based BC prediction models in a prospective cohort of women from the Million Veteran Program.

Effects of early daily alcohol exposure on placental function and fetal growth in a rhesus macaque model.

Background: Prenatal alcohol exposure is the most common cause of birth defects and intellectual disabilities and can increase the risk of stillbirth and negatively impact fetal growth.

Objective: To determine the effect of early prenatal alcohol exposure on nonhuman primate placental function and fetal growth. We hypothesized that early chronic prenatal alcohol would alter placental perfusion and oxygen availability that adversely affects fetal growth.

Adolescent novelty seeking is associated with greater ventral striatal and prefrontal brain response during evaluation of risk and reward.

Adolescence is a period during which reward sensitivity is heightened. Studies suggest that there are individual differences in adolescent reward-seeking behavior, attributable to a variety of factors, including temperament. This study investigated the neurobiological underpinnings of risk and reward evaluation as they relate to self-reported pleasure derived from novel experiences on the revised Early Adolescent Temperament Questionnaire (EATQ-R).

More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY.

Objective: To report the final long-term safety and efficacy analyses of patients with acromegaly treated with pegvisomant from the ACROSTUDY.

Design: Global (15 countries), multicentre, non-interventional study (2004-2017).

Methods: The complete ACROSTUDY cohort comprised patients with acromegaly, who were being treated with pegvisomant (PEGV) prior to the study or at enrolment.

Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study.

Background: Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumors (GISTs) as at least fourth-line therapy. In INVICTUS, ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.

Sex Differences in the Brain Transcriptome Related to Alcohol Effects and Alcohol Use Disorder.

There is compelling evidence that sex and gender have crucial roles in excessive alcohol (ethanol) consumption. Here, we review some of the data from the perspective of brain transcriptional differences between males and females, focusing on rodent animal models. A key emerging transcriptional feature is the role of neuroimmune processes.

Sex-specific patterns of white matter microstructure are associated with emerging depression during adolescence.

Prior research has demonstrated associations between adolescent depression and alterations in the white matter microstructure of fiber tracts implicated in emotion regulation. Using diffusion tensor imaging, this study explored premorbid, sex-specific white matter microstructural features that related to future emergence of major depressive disorder (MDD) during adolescence and young adulthood. Adolescents from the National Consortium on Alcohol and Neurodevelopment in Adolescence study, who were 12-21 years old at study entry and had not experienced major depression as of the baseline assessment, were selected for inclusion (N = 462, n = 223 female adolescents).

Cumulative comorbidity burden does not worsen outcomes in management of chronic rhinosinusitis.

Background: The impact of multiple coexisting medical comorbidities on treatment outcomes in chronic rhinosinusitis (CRS) is unknown. In this study we sought to evaluate the effect of comorbidities on sinonasal quality of life (QOL) and general health utility values by utilizing the Functional Comorbidity Index (FCI) in CRS patients.

Methods: Patients with CRS were prospectively enrolled in a cross-sectional study of medical and surgical therapies.

Mapping the Molecular Architecture Required for Lipid-Binding Pockets Using a Subset of Established and Orphan G-Protein Coupled Receptors.

G-protein coupled receptors (GPCRs) sense a wide variety of stimuli, including lipids, and transduce signals to the intracellular environment to exert various physiological responses. However, the structural features of GPCRs responsible for detecting and triggering responses to distinct lipid ligands have only recently begun to be revealed. 14,15-epoxyeicosatrienoic acid (14,15-EET) is one such lipid mediator that plays an essential role in the vascular system, displaying both vasodilatory and anti-inflammatory properties.

Long-term alcohol drinking in High Drinking in the Dark mice is stable for many months and does not show alcohol deprivation effects.

We have modelled genetic risk for binge-like drinking by selectively breeding High Drinking in the Dark-1 and -2 (HDID-1 and HDID-2) mice for their propensity to reach intoxicating blood alcohol levels (BALs) after binge-like drinking in a single bottle, limited access paradigm. Interestingly, in standard two-bottle choice (2BC) tests for continuously available alcohol versus water, HDID mice show modest levels of preference. This indicates some degree of independence of the genetic contributions to risk for binge-like and sustained, continuous access drinking.