G protein-coupled receptor modulation of striatal dopamine transmission: Implications for psychoactive drug effects.

Dopamine transmission in the striatum is a critical mediator of the rewarding and reinforcing effects of commonly misused psychoactive drugs. G protein-coupled receptors (GPCRs) that bind a variety of neuromodulators including dopamine, endocannabinoids, acetylcholine and endogenous opioid peptides regulate dopamine release by acting on several components of dopaminergic circuitry. Striatal dopamine release can be driven by both somatic action potential firing and local mechanisms that depend on acetylcholine released from striatal cholinergic interneurons. GPCRs that primarily regulate somatic firing of dopamine neurons via direct effects or modulation of synaptic inputs are likely to affect distinct aspects of behaviour and psychoactive drug actions compared with those GPCRs that primarily regulate local acetylcholine-dependent dopamine release in striatal regions. This review will highlight mechanisms by which GPCRs modulate dopaminergic transmission and the relevance of these findings to psychoactive drug effects on physiology and behaviour.

Rapid and highly efficient morphogenic gene-mediated hexaploid wheat transformation.

The successful employment of morphogenic regulator genes, Zm-Baby Boom (ZmBbm) and Zm-Wuschel2 (ZmWus2), for Agrobacterium-mediated transformation of maize (Zea mays L.) and sorghum (Sorghum bicolor L.) has been reported to improve transformation by inducing rapid somatic embryo formation. Here, we report two morphogenic gene-mediated wheat transformation methods, either with or without morphogenic and marker gene excision. These methods yield independent-transformation efficiency up to 58% and 75%, respectively. In both cases, the tissue culture duration for generating transgenic plants was significantly reduced from 80 to nearly 50 days. In addition, the transformation process was significantly simplified to make the procedure less labor-intensive, higher-throughput, and more cost-effective by eliminating the requirement for embryonic axis excision, bypassing the necessity for prolonged dual-selection steps for callus formation, and obviating the prerequisite of cytokinin for shoot regeneration. Furthermore, we have demonstrated the flexibility of the methods and generated high-quality transgenic events across multiple genotypes using herbicide (phosphinothricin, ethametsulfuron)- and antibiotic (G418)-based selections.

Implementing a patient acuity tool: Perceived effectiveness for more equitable staff assignments.

PURPOSE: This study aimed to assess the acceptability, relevance, and effectiveness of a patient acuity tool (PAT) among part-time and full-time RNs. METHODS: A pre- and post-test intervention was used to evaluate a PAT among part-time and full-time RNs on a 28-bed telemetry unit at a Magnet®-designated hospital. An eight-item PAT questionnaire measured nurse acceptability. Relevance was evaluated using the RN Opinion of Relevance of Concepts of the PAT Questionnaire, and effectiveness was evaluated using the RN Opinion of Effectiveness of the PAT Questionnaire. RESULTS: A total of 22/33 (66.6%) RNs participated and completed the PAT questionnaire that measured nurse acceptability of the PAT assessment process. Statistically significant differences were demonstrated between two out of eight variables pre-post intervention; "the way we currently evaluate patient acuity assists the charge nurse in making nurse-patient assignments" (t 3.070, df 22, P = .006), "the way we currently evaluate patient acuity is an accurate assessment of acuity" (t 2.390, df 22, P = .026). CONCLUSION: Acuity tools should be specific for a nursing unit and adapt to staffing and patient needs, which can include a change in a patient's condition, unexpected discharges and/or admissions, and psychosocial components.

Local modulation by presynaptic receptors controls neuronal communication and behaviour.

Central nervous system neurons communicate via fast synaptic transmission mediated by ligand-gated ion channel (LGIC) receptors and slower neuromodulation mediated by G protein-coupled receptors (GPCRs). These receptors influence many neuronal functions, including presynaptic neurotransmitter release. Presynaptic LGIC and GPCR activation by locally released neurotransmitters influences neuronal communication in ways that modify effects of somatic action potentials. Although much is known about presynaptic receptors and their mechanisms of action, less is known about when and where these receptor actions alter release, especially in vivo. This Review focuses on emerging evidence for important local presynaptic receptor actions and ideas for future studies in this area.

Prefrontal cortex parvalbumin interneurons exhibit decreased excitability and potentiated synaptic strength after ethanol reward learning.

The prefrontal cortex (PFC) is intimately associated with behavioral characteristics of alcohol use disorders, including high motivation to drink and difficulty with moderation. Thus, continued mechanistic research investigating PFC cells and targets altered by ethanol experiences should inform translational efforts to craft new, efficacious treatments. Inhibitory interneurons expressing parvalbumin (PV-INs) comprise only a minor fraction of cells within the PFC, yet these cells are indispensable for coordinating PFC ensemble function, oscillatory activity, and subcortical output. Based on this, PV-INs represent an exciting target for the rational design of breakthrough treatments for alcohol use disorders. Here, we assessed experience-dependent physiological adaptations via ethanol place conditioning. By manipulating the timing of administration relative to conditioning sessions, equivalent ethanol exposure can form either rewarding or aversive memories in different individuals. Here, we found that female mice and male mice on a C57BL/6J background display conditioned place preference (CPP) or aversion (CPA) to an intoxicating dose of ethanol (2 g/kg, intraperitoneal [i.p.]) without overt differences between sexes. Ethanol reward learning was associated with decreased PV-IN excitability in deep layer prelimbic PFC, whereas PV-INs from CPA mice were not different from controls. Furthermore, PV-INs from mice in the CPP group, but not the CPA group, displayed potentiated excitatory synaptic strength that emerged during 1 week of abstinence. Taken together, these findings illustrate that synaptic and intrinsic adaptations associated with ethanol can depend on an individual's experience. These studies provide further context and support for PFC PV-INs as intriguing targets for modulating alcohol associations.

Leading the Development of a Network-Wide Professional Practice Model: The Role of the Contemporary Nurse Executive.

The health care settings of today are rapidly evolving in form and function, challenging nurse executives to adopt, adapt, and develop new ways to lead and find professional fulfillment in their roles. The organizational design of many health care settings has changed from a functional to a matrix structure to facilitate more effective and efficient operations. While the structures and reporting relationship of contemporary nurse executives may have changed significantly, the primary responsibility of championing the advancement of the profession of nursing remains essential. The mastery of change management methods is critical for the nurse executive to successfully lead in today's dynamic health care settings. A well-developed and actualized nursing professional practice model is a foundational tool for the nurse executive to employ to advance the profession of nursing in any health care setting or structure. This article describes how a nurse executive used change management methods and principles to lead the development of a new network-wide unifying nursing professional practice model in a highly matrixed health care setting.

A person centered nursing care intervention on a medical surgical unit.

When a patient is admitted to a hospital, admission assessments are completed in the electronic medical record. There is minimal information about who the person is, what they liked to be called, favorite activity, and or past occupation to view. A communication board is visible to all caring for the patient. This pre-post design evaluated whether using "All About Me Board" (AAMB) could change workplace climate perception among 25 registered nurses (RN)s in a 28 bed medical surgical unit. RNs were asked to participate in a Person Centered Climate Questionnaire and were provided education about purpose and use of the AAMB, which were placed in each patient's room. Having the AAMB placed and visible in patient rooms provided healthcare providers personal information to assist in planning care with patients and family. Survey results were favorable in supporting a workplace environment where patients were empowered to participate in planning their care.

A Novel Large Scale Integrated Telemonitoring Program for COVID-19.

Introduction: Coronavirus disease 2019 (COVID-19) has forced health care systems to rethink the optimal delivery of health care services and has dramatically increased demand for general medicine providers (internal medicine, family medicine, emergency medicine), while simultaneously reducing demand for many subspecialty services. At Kaiser Permanente, we implemented a program wherein health care providers drawn from multiple disciplines perform daily telemedicine check-ins on COVID-19 patients, allowing us to both maintain social distancing and make use of providers in specialties who otherwise may have had lower in-clinic volumes. Methods: Kaiser Permanente patients testing positive for COVID-19 between March and October 2020 were referred to our program. Physicians and nurses (RNs) were invited to participate in our program and were trained using Microsoft Teams™ meetings. Patients receive daily phone calls by a physician or RN. Select patients receive portable pulse oximeter devices based on standardized criteria incorporating age and comorbidities. When patients are determined to be clinically stable, they are discharged back to their primary care physician for ongoing management. Results: Descriptive results for the virtual home care program (VHCP) are reported through October 2020, though these results do not represent a planned statistical analysis. Forty-two percent of the patients were male, 43% were black, and 30% were Hispanic. The most common comorbidities of patients in our program were obesity (body mass index >30 kg/m2; 35%), followed by hypertension (32%) and diabetes mellitus (19%). Then, 8.2% of patients ultimately required hospital admission. Mortality rate for patients in our program was 1.33%. Discussion: Our program was able to provide virtual care for thousands of COVID-19 positive Kaiser members in the Washington, DC, and Baltimore Metro regions. We did so by utilizing physicians and RNs from specialties experiencing a decrease in clinic volume attributable to the COVID-19 pandemic. The experiences of our program may be valuable to clinicians wishing to establish similar programs of their own.

Genotype-Independent Transformation and Genome Editing of Brassica napus Using a Novel Explant Material.

Agrobacterium-mediated transformation of canola (Brassica napus) via hypocotyl segments has been a commonly used method for the past 30 years. While the hypocotyl-based method is well-established, it is not readily adapted to elite germplasm and the prolonged process is not ideal for a production transformation setting. We developed an Agrobacterium-mediated transformation method based on epicotyl and higher stem (internodal) segments that is efficient, rapid and amenable for high-throughput transformation and genome editing. The method has been successfully implemented in multiple canola genotypes. The method appears to be genotype-independent, with varying transformation efficiencies. Internodal segment transformation was used to generate transgenic events as well as CRISPR-Cas9-mediated frameshift gene knockouts.

Allosteric modulation of metabotropic glutamate receptors in alcohol use disorder: Insights from preclinical investigations.

Metabotropic glutamate (mGlu) receptors are family C G protein-coupled receptors (GPCRs) that modulate neuronal excitability and synaptic transmission throughout the nervous system. Owing to recent advances in development of subtype-selective allosteric modulators of mGlu receptors, individual members of the mGlu receptor family have been proposed as targets for treating a variety of neurological and psychiatric disorders, including substance use disorders. In this chapter, we highlight preclinical evidence that allosteric modulators of mGlu receptors could be useful for reducing alcohol consumption and preventing relapse in alcohol use disorder (AUD). We begin with an overview of the preclinical models that are used to study mGlu receptor involvement in alcohol-related behaviors. Alcohol exposure causes adaptations in both expression and function of various mGlu receptor subtypes, and pharmacotherapies aimed at reversing these adaptations have the potential to reduce alcohol consumption and seeking. Positive allosteric modulators (PAMs) of mGlu2 and negative allosteric modulators of mGlu5 show particular promise for reducing alcohol intake and/or preventing relapse. Finally, this chapter discusses important considerations for translating preclinical findings toward the development of clinically useful drugs, including the potential for PAMs to avoid tolerance issues that are frequently observed with repeated administration of GPCR agonists.

Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2.

Dorsal striatal manipulations including stimulation of dopamine release and activation of medium spiny neurons (MSNs) are sufficient to drive reinforcement-based learning. Glutamatergic innervation of the striatum by the cortex and thalamus is a critical determinant of MSN activity and local regulation of dopamine release. However, the relationship between striatal glutamatergic afferents and behavioral reinforcement is not well understood. We evaluated the reinforcing properties of optogenetic stimulation of thalamostriatal terminals, which are associated with vesicular glutamate transporter 2 (Vglut2) expression, in the dorsomedial striatum (DMS), a region implicated in goal-directed behaviors. In mice expressing channelrhodopsin-2 (ChR2) under control of the Vglut2 promoter, optical stimulation of the DMS reinforced operant lever-pressing behavior. Mice also acquired operant self-stimulation of thalamostriatal terminals when ChR2 expression was virally targeted to the intralaminar thalamus. Stimulation trains that supported operant responding evoked dopamine release in the DMS and excitatory postsynaptic currents in DMS MSNs. Our previous work demonstrated that the presynaptic G protein-coupled receptor metabotropic glutamate receptor 2 (mGlu2) robustly inhibits glutamate and dopamine release induced by activation of thalamostriatal afferents. Thus, we examined the regulation of thalamostriatal self-stimulation by mGlu2. Administration of an mGlu2/3 agonist or an mGlu2-selective positive allosteric modulator reduced self-stimulation. Conversely, blockade of these receptors increased thalamostriatal self-stimulation, suggesting that endogenous activation of these receptors negatively modulates the reinforcing properties of thalamostriatal activity. These findings demonstrate that stimulation of thalamic terminals in the DMS is sufficient to reinforce a self-initiated action, and that thalamostriatal reinforcement is constrained by mGlu2 activation.

Age-dependent impairment of metabotropic glutamate receptor 2-dependent long-term depression in the mouse striatum by chronic ethanol exposure.

Chronic alcohol exposure is associated with increased reliance on behavioral strategies involving the dorsolateral striatum (DLS), including habitual or stimulus-response behaviors. Presynaptic G protein-coupled receptors (GPCRs) on cortical and thalamic inputs to the DLS inhibit glutamate release, and alcohol-induced disruption of presynaptic GPCR function represents a mechanism by which alcohol could disinhibit DLS neurons and thus bias toward use of DLS-dependent behaviors. Metabotropic glutamate receptor 2 (mGlu2) is a Gi/o-coupled GPCR that robustly modulates glutamate transmission in the DLS, inducing long-term depression (LTD) at both cortical and thalamic synapses. Loss of mGlu2 function has recently been associated with increased ethanol seeking and consumption, but the ability of alcohol to produce adaptations in mGlu2 function in the DLS has not been investigated. We exposed male C57Bl/6J mice to a 2-week chronic intermittent ethanol (CIE) paradigm followed by a brief withdrawal period, then used whole-cell patch clamp recordings of glutamatergic transmission in the striatum to assess CIE effects on mGlu2-mediated synaptic plasticity. We report that CIE differentially disrupts mGlu2-mediated long-term depression in the DLS vs. dorsomedial striatum (DMS). Interestingly, CIE-induced impairment of mGlu2-LTD in the dorsolateral striatum is only observed when alcohol exposure occurs during adolescence. Incubation of striatal slices from CIE-exposed adolescent mice with a positive allosteric modulator of mGlu2 fully rescues mGlu2-LTD. In contrast to the 2-week CIE paradigm, acute exposure of striatal slices to ethanol concentrations that mimic ethanol levels during CIE exposure fails to disrupt mGlu2-LTD. We did not observe a reduction of mGlu2 mRNA or protein levels following CIE exposure, suggesting that alcohol effects on mGlu2 occur at the functional level. Our findings contribute to growing evidence that adolescents are uniquely vulnerable to certain alcohol-induced neuroadaptations, and identify enhancement of mGlu2 activity as a strategy to reverse the effects of adolescent alcohol exposure on DLS physiology.

Memory matters in dementia: Efficacy of a mobile reminiscing therapy app.

INTRODUCTION: Reminiscence therapy has been shown to improve mental health and quality of life in dementia; however, reminiscence therapy is often delivered by therapists instead of being technology-enabled. This study evaluated the preliminary efficacy of Memory Matters (MM), an iPad reminiscence game on mood, social interaction, quality of life, and behavioral and psychological symptoms of dementia. METHODS: This pilot study used an experimental design where participants were randomized on a 2:2:1 ratio to three arms: individual MM (one-on-one with an interventionist), group MM (2-3 participants per session), or waitlist control. MM was delivered for 30 minutes a session, twice a week for six weeks, followed by six-week self-play. Outcomes were assessed at the baseline, six weeks, and 12 weeks by data collectors blinded to group allocation. Data were analyzed using intention-to-treat analysis and analysis of covariance. RESULTS: The sample (n = 80) was 82.1 ± 7.8 years in age with 58% female, 15.3 ± 3.3 years of education. Mood did not differ, except for apathetic mood between group MM and control arm at 12 weeks (P = .051). Social interaction improved for individual MM compared with group MM (t = 2.38, P = .017) and control (t = 2.84, P = .005) at six weeks, but not 12 weeks. Other outcomes did not differ. DISCUSSION: MM improved social interaction and possibly mood. Future studies are needed to evaluate the efficacy of MM with a sufficient sample size.

Optimize patient outcomes among females undergoing gynecological surgery: A randomized controlled trial.

BACKGROUND: Optimizing early education in gynecological procedures utilizing an Enhanced Recovery after Surgery (ERAS) program and a bundle concept may optimize patient outcomes after surgery. PURPOSE: Evaluate whether an ERAS bundle compared to standard education can affect length of stay, 30 day readmission, and patient satisfaction among patients undergoing gynecologic surgery. DESIGN: Prospective, comparative, randomized design SETTING: 28 bed Medical Surgical Unit SAMPLE/INTERVENTION: 50 patients undergoing hysterectomy, 25 who received post-operative evidence based bundle/standard education, and 25 who received standard education packet. Bundle components included 1) early mobilization, 2) early transition to oral pain medication, 3) early feeding, and 4) chewing gum. A follow-up phone call was made in two to three days following discharge for both groups utilizing teach-back. RESULTS: 84% (n = 21) patients in the bundle group were discharged in one day. There were no 30 day readmissions for both groups. Twenty two (88%) participants met the bundle components 100% of the time. For the indicator "walking helped with recovery" 100% (n = 25) responded "very good to excellent" for bundle group and 96% (n = 24) responded "very good to excellent" for standard group. Twenty three (92%) of the bundle group felt that that overall nursing care received was very good to excellent and 24 (96%) of the general group felt that overall nursing care received was very good to excellent. CONCLUSION: Optimizing peri-operative education using a bundle approach to provide evidence based interventions can minimize risk and enhance early recovery for females undergoing gynecological surgery.

Active Zone Proteins RIM1αß Are Required for Normal Corticostriatal Transmission and Action Control.

Dynamic regulation of synaptic transmission at cortical inputs to the dorsal striatum is considered critical for flexible and efficient action learning and control. Presynaptic mechanisms governing the properties and plasticity of glutamate release from these inputs are not fully understood, and the corticostriatal synaptic processes that support normal action learning and control remain unclear. Here we show in male and female mice that conditional deletion of presynaptic proteins RIM1αß (RIM1) from excitatory cortical neurons impairs corticostriatal synaptic transmission in the dorsolateral striatum. Key forms of presynaptic G-protein-coupled receptor-mediated short- and long-term striatal plasticity are spared following RIM1 deletion. Conditional RIM1 KO mice show heightened novelty-induced locomotion and impaired motor learning on the accelerating rotarod. They further show heightened self-paced instrumental responding for food and impaired learning of a habitual instrumental response strategy. Together, these findings reveal a selective role for presynaptic RIM1 in neurotransmitter release at prominent basal ganglia synapses, and provide evidence that RIM1-dependent processes help to promote the refinement of skilled actions, constrain goal-directed behaviors, and support the learning and use of habits.SIGNIFICANCE STATEMENT Our daily functioning hinges on the ability to flexibly and efficiently learn and control our actions. How the brain encodes these capacities is unclear. Here we identified a selective role for presynaptic proteins RIM1αß in controlling glutamate release from cortical inputs to the dorsolateral striatum, a brain structure critical for action learning and control. Behavioral analysis of mice with restricted genetic deletion of RIM1αß further revealed roles for RIM1αß-dependent processes in the learning and refinement of motor skills and the balanced expression of goal-directed and habitual actions.

Music intervention to prevent delirium among older patients admitted to a trauma intensive care unit and a trauma orthopaedic unit.

PURPOSE: Evaluate music listening for delirium prevention among patients admitted to a Trauma Intensive Care and Trauma Orthopaedic Unit. The Roy Adaptation Model provided the theoretical framework focusing on modifying contextual stimuli. METHODS: Randomised controlled trial, 40 patients aged 55 and older. INTERVENTION: Participants randomly assigned to receive music listening or usual care for 60 minutes, twice a day, over three days. Pre-recorded self-selected music using an iPod and headsets, with slow tempo, low pitch and simple repetitive rhythms to alter physiologic responses. OUTCOMES: Heart rate, respiratory rate, systolic and diastolic blood pressure, confusion assessment method. RESULTS: Repeated measures ANOVA, F(4, 134) = 4.75, p = .001, suggested statistically significant differences in heart rate pre/post music listening, and F(1, 37) = 10.44, p = .003 in systolic blood pressure pre/post music listening. Post-hoc analysis reported changes at three time periods of statistical significance; (p = .010), (p = .005) and (p = .039) and a change in systolic blood pressure pre/post music listening; (p = .001) of statistical significance. All participants screened negative for delirium. CONCLUSION: Music addresses pathophysiologic mechanisms that contribute to delirium; neurotransmitter imbalance, inflammation and acute physiologic stressors. Music to prevent delirium is one of few that provide support in a critical care setting.