Constitutive internalisation of EP2 differentially regulates G protein signalling.

The prostanoid G protein-coupled receptor (GPCR) EP2 is widely expressed and implicated in endometriosis, osteoporosis, obesity, pre-term labour and cancer. Internalisation and intracellular trafficking are critical for shaping GPCR activity, yet little is known regarding the spatial programming of EP2 signalling and whether this can be exploited pharmacologically. Using three EP2-selective ligands that favour activation of different EP2 pathways, we show that EP2 undergoes limited agonist-driven internalisation but is constitutively internalised via dynamin-dependent, β-arrestin-independent pathways.

Different factors identified by stakeholder group for barriers and facilitators to measurement-based care implementation in behavioral health clinics.

Introduction: Despite the benefits of measurement-based care (MBC) in the behavioral health setting, there have been difficulties in implementation and low saturation. Although barriers and facilitators to MBC implementation have been identified, research has generally only included the perspective of one stakeholder group. The current study aims to examine the similarities and differences-by stakeholder group-in the identified barriers to and facilitators of implementing MBC in the behavioral health setting.

Bilingual randomized controlled trial design, of a telephone-based intervention to promote rehabilitation adherence; A study focus on recruitment of Hispanic children with traumatic brain injury.

Background: While Hispanic children experience large long-term disparities in disability after traumatic Brain Injury (TBI), there is a gap in evidenced-based interventions to improve outcomes among this rapidly growing and at high-risk population. We developed and pilot tested a bilingual/bicultural intervention informed by Hispanic families consisting of Brain Injury Education and outpatient Navigation (1st BIEN). It integrates bilingual in-person education enriched by video content delivered through mobile phone devices, with outpatient navigation by bilingual and bicultural navigators during transitions of care and school return.

First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t.

Web-Based Survey Piloting Process as a Model for Developing and Testing Past Contraceptive Use and Pregnancy History: Cystic Fibrosis Case Study.

Background: Individuals with complex, chronic diseases are now living longer, making reproductive health an important topic to address in the health care setting. Self-respondent surveys are a feasible way to collect past contraceptive use and pregnancy history to assess contraceptive safety and effectiveness. Because sensitive topics, such as contraception and pregnancy outcomes, can vary across social groups or cultures, piloting questions and evaluating survey administration procedures in the target population are necessary for precise and reliable responses before wide distribution.

A Manualized Behavioral Therapy Intervention for Youth with Autism Spectrum Disorder and Substance Use Disorder.

Research highlights the increasing overlap of autism spectrum disorder and substance use disorders in young people. However, no behavioral treatments exist addressing this comorbidity despite great need. A team of clinicians developed an integrated behavioral protocol addressing substance use in youth with autism spectrum disorder.

A systematic review of substance use screening in outpatient behavioral health settings.

Objective: Despite the frequent comorbidity of substance use disorders (SUDs) and psychiatric disorders, it remains unclear if screening for substance use in behavioral health clinics is a common practice. The aim of this review is to examine what is known about systematic screening for substance use in outpatient behavioral health clinics.

Methods: We conducted a PRISMA-based systematic literature search assessing substance use screening in outpatient adult and pediatric behavioral health settings in PubMed, Embase, and PsycINFO.

Examining the clinical correlates of conduct disorder in youth with bipolar disorder.

Background: Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD.

Methods: 357 subjects with BP were derived from two independent datasets of youth with and without BP.

Bimatoprost promotes satiety and attenuates body weight gain in rats fed standard or obesity-promoting diets.

Bimatoprost is a synthetic prostamide F analog that down-regulates adipogenesis in vitro. This effect has been attributed to participation in a negative feedback loop that regulates anandamide-induced adipogenesis. A follow-on investigation has now been conducted into the broader metabolic effects of bimatoprost using rats under both normal state and obesity-inducing conditions.

The relationship between shame, perfectionism and Anorexia Nervosa: A grounded theory study.

Objectives: The aim of this study was to explore the potential relationship between shame, perfectionism and Anorexia Nervosa (AN) and their impact on recovery from AN.

Method: Semi-structured interviews were conducted with 11 people currently accessing services for AN. Interviews were transcribed and analysed using constructivist-grounded theory methodology.

Functional rewiring of G protein-coupled receptor signaling in human labor.

Current strategies to manage preterm labor center around inhibition of uterine myometrial contractions, yet do not improve neonatal outcomes as they do not address activation of inflammation. Here, we identify that during human labor, activated oxytocin receptor (OTR) reprograms the prostaglandin E2 receptor, EP2, in the pregnant myometrium to suppress relaxatory/Gαs-cAMP signaling and promote pro-labor/inflammatory responses via altered coupling of EP2 from Gαq/11 to Gαi/o. The ability of EP2 to signal via Gαi/o is recapitulated with in vitro OT and only following OTR activation, suggesting direct EP2-OTR crosstalk.

Methodological Strategies for Prospective Harmonization of Studies: Application to 10 Distinct Outcomes Studies of Preventive Interventions Targeting Opioid Misuse.

The Helping to End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is rapidly developing 10 distinct evidence-based interventions for implementation in a variety of settings to prevent opioid misuse and opioid use disorder. One HPC objective is to compare intervention impacts on opioid misuse initiation, escalation, severity, and disorder and identify whether any HPC interventions are more effective than others for types of individuals. It provides a rare opportunity to prospectively harmonize measures across distinct outcomes studies.

Coverage Score: A Model Agnostic Method to Efficiently Explore Chemical Space.

Selecting the most appropriate compounds to synthesize and test is a vital aspect of drug discovery. Methods like clustering and diversity present weaknesses in selecting the optimal sets for information gain. Active learning techniques often rely on an initial model and computationally expensive semi-supervised batch selection.

Parental perspectives on attention-deficit/hyperactivity disorder treatments for children.

This study investigated parental perspectives and experiences on the evaluation and treatment process associated with attention-deficit/hyperactivity disorder (ADHD). Five hundred sixty-eight parents of youth 2-28 years-old (M = 9.37; SD = 4.

The Impact of Pharmacotherapy of Childhood-Onset Psychiatric Disorders on the Development of Substance Use Disorders.

Child- and adolescent-onset psychopathology is known to increase the risk for developing substance use and substance use disorders (SUDs). While pharmacotherapy is effective in treating pediatric psychiatric disorders, the impact of medication on the ultimate risk to develop SUDs in these youth remains unclear. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of peer-reviewed literature published on PubMed through November 2021, examining pharmacological treatments of psychiatric disorders in adolescents and young adults and their effect on substance use, misuse, and use disorder development.

Characterizing autistic traits in treatment-seeking young adults with substance use disorders.

Background And Objectives: Recent work highlights an increase in the overlap of autism spectrum disorder (ASD) and substance use disorder (SUD). Little is known about the presence of ASD symptoms in SUD-treatment-seeking populations.

Methods: The informant-rated Social Responsiveness Scale-2 (SRS-2) was completed at intake to an outpatient SUD clinic for youth aged 16-26 (N = 69).

Thick bark can protect trees from a severe ambrosia beetle attack.

Thick bark has been shown to protect trees from wildfires, but can it protect trees from an ambrosia beetle attack? We addressed this question by examining the distribution of holes of the invasive Kuroshio Shot Hole Borer (KSHB, ; Coleoptera: Scolytinae) in the bark of Goodding's black willow (), one of the KSHB's most-preferred hosts. The study was conducted in the Tijuana River Valley, California, in 2016-17, during the peak of the KSHB infestation there. Using detailed measurements of bark samples cut from 27 infested trees, we tested and found support for two related hypotheses: (1) bark thickness influences KSHB attack densities and attack locations, i.

Deletion of the gene encoding prostamide/prostaglandin F synthase reveals an important role in regulating intraocular pressure.

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F and prostaglandin F (PGF). The importance of this enzyme, relative to the aldo-keto reductase (AKR) series, in providing functional tissue prostamide F levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (Fam213b / Prxl2b) was accomplished by a two exon disruption.

A Second Generation Prostanoid Receptor Antagonist Acting at Multiple Receptor Subtypes.

It has previously been reported that a prototypical compound (AGN 211377), which blocks pro-inflammatory prostanoid receptors (DP, DP, EP, EP FP, TP) and leaves open IP and EP receptors so that their anti-inflammatory properties could be exerted, produced superior inhibitory effects on cytokine release from human macrophages compared to cyclooxygenase (COX) inhibitors. This favorable activity profile translated into animal studies, with AGN 211377 exceeding the level of inhibition afforded by COX inhibition. AGN 211377 was not, however, a practical drug candidate, having poor bioavailability and cost of goods concerns.

The role of EP receptors in mediating the ultra-long-lasting intraocular pressure reduction by JV-GL1.

Background: A single application of JV-GL1 substantially lowers non-human primate intraocular pressure (IOP) for about a week, independent of dose. This highly protracted effect does not correlate with its ocular biodisposition or correlate with the once-daily dosing regimen for other prostanoid EP receptor agonists such as trapenepag or omidenepag. The underlying pharmacological mechanism for the multiday extended activity of JV-GL1 is highly intriguing.

A Preliminary Characterisation of Innovative Semi-Flexible Composite Pavement Comprising Geopolymer Grout and Reclaimed Asphalt Planings.

This article considers semi-flexible composite (SFC) pavement materials made with reclaimed asphalt planings (RAP) and geopolymer cement-based grouts. Geopolymer grouts were developed and used to fill the internal void structure of coarse RAP skeletons with varying levels of porosity. The geopolymer grouts were formulated at ambient temperature using industrial by-products to offer economic and environmental savings relative to conventional Portland cement-based grouting systems.