Quality improvement projects conducted by interprofessional teams of learners: Implementation and impact.

Students in their second year of the Vanderbilt Program of Interprofessional Learning (VPIL) complete team-based quality improvement (QI) projects in their assigned clinic as part of the core curriculum. This report describes the creation and implementation of the student teams' QI curriculum and investigates how clinical preceptors view the project impact. Between 2012-2019, the VPIL teams designed and implemented 69 improvement projects. Improvement projects fell primarily into three categories: improving clinic care delivery (n = 25, 36%), patient education and health coaching (n = 21, 30%), and quality measures such as screening tests/prophylaxis (n = 10, 14%). Clinic preceptors received a survey about the sustainability and effectiveness of the projects. Survey feedback was received from 44/69 (64%) preceptors. Many (70%) projects resulted in perceived improvements, and some projects (34%) had improvements that are still in use. Despite barriers and challenges, interprofessional student teams can successfully learn the basics of QI and work together to design and implement a project. These projects have the potential to make meaningful changes in clinic practices and are helpful to the clinic preceptors.

Desire or Dread from Nucleus Accumbens Inhibitions: Reversed by Same-Site Optogenetic Excitations.

Microinjections of a glutamate AMPA antagonist (DNQX) in medial shell of nucleus accumbens (NAc) can cause either intense appetitive motivation (i.e., 'desire') or intense defensive motivation (i.e., 'dread'), depending on site along a flexible rostrocaudal gradient and on environmental ambience. DNQX, by blocking excitatory AMPA glutamate inputs, is hypothesized to produce relative inhibitions of NAc neurons. However, given potential alternative explanations, it is not known whether neuronal inhibition is in fact necessary for NAc DNQX microinjections to generate motivations. Here we provide a direct test of whether local neuronal inhibition in NAc is necessary for DNQX microinjections to produce either desire or dread. We used optogenetic channelrhodopsin (ChR2) excitations at the same local sites in NAc as DNQX microinjections to oppose relative neuronal inhibitions induced by DNQX in female and male rats. We found that same-site ChR2 excitation effectively reversed the ability of NAc DNQX microinjections to generate appetitive motivation, and similarly reversed ability of DNQX microinjections to generate defensive motivation. Same-site NAc optogenetic excitations also attenuated recruitment of Fos expression in other limbic structures throughout the brain, which was otherwise elevated by NAc DNQX microinjections that generated motivation. However, to successfully reverse motivation generation, an optic fiber tip for ChR2 illumination needed to be located within <1 mm of the corresponding DNQX microinjector tip; that is, both truly at the same NAc site. Thus, we confirm that localized NAc neuronal inhibition is required for AMPA-blocking microinjections in medial shell to induce either positively-valenced 'desire' or negatively-valenced 'dread'.SIGNIFICANCE STATEMENT A major hypothesis posits neuronal inhibitions in nucleus accumbens generate intense motivation. Microinjections in nucleus accumbens of glutamate antagonist, DNQX, which might suppress local neuronal firing, generate either appetitive or defensive motivation, depending on site and environmental factors. Is neuronal inhibition in nucleus accumbens required for such pharmacologically-induced motivations? Here we demonstrate that neuronal inhibition is necessary to generate appetitive or defensive motivations, using local optogenetic excitations to oppose putative DNQX-induced inhibitions. We show that excitation at the same site prevents DNQX microinjections from recruiting downstream limbic structures into neurobiological activation, and simultaneously prevents generation of either appetitive or defensive motivated behaviors. These results may be relevant to roles of nucleus accumbens mechanisms in pathological motivations, including addiction and paranoia.

Social influences on morphine conditioned place preference in adolescent mice.

Social/peer influences are among the strongest predictors of adolescent drug use. However, this important subject does not get much attention in pre-clinical studies. We recently observed that exposure to different social partners modulates morphine locomotor sensitization. Sensitivity to the hyper-locomotor response of drugs of abuse is a predictor of sensitivity to other drug-induced behaviors. Thus, this study examined how exposure to different social partners affected the rewarding properties of morphine. All animals were group-housed four per cage in one of two conditions referred to as 'only' and 'cage-mates'. In the mixed treatment condition, morphine- and saline-treated mice were housed together. These groups are referred to as 'morphine cage-mates' and 'saline cage-mates', respectively. In the separated treatment conditions, all mice in the cage received morphine (i.e. 'morphine only') or saline (i.e. 'saline only'), and cages were visually separated from each other. All animals were subsequently individually tested for the acquisition of morphine conditioned place preference (CPP) following one conditioning session with 10, 20 or 40 mg/kg morphine or saline. As expected, one conditioning session established morphine CPP in the morphine only animals, but not in the saline only animals. Notably, morphine CPP was not acquired by the morphine cage-mate animals. Additionally, 40 mg/kg morphine was sufficient to establish morphine CPP in the saline cage-mate animals. These results indicate that social environment has an effect on the rewarding properties of morphine. It suggests that exposure to different peers can alter the abuse potential of opioids and potentially other illicit drugs.

The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes.

Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes.

Dissecting Mechanisms of Motivation within the Nucleus Accumbens Using Optogenetics.

Studies mapping psychological functions to discrete brain regions often require manipulations that yield changes in a particular area and observing a subsequent shift in behavior. As investigators tap into neural underpinnings of behavior, it is useful to utilize technologies that permit temporally and spatially discrete shifts in neural signaling and neurobiological processes. This chapter contains protocols for creating "Fos plumes," a means of mapping alterations in neural activity induced by neural manipulations. By localizing increases or decreases in c-Fos in targeted brain regions, the relative spread of each manipulation can be mapped, and the functional roles of individual mechanisms within particular brain areas can be defined. The chapter also provides examples of behavioral testing protocols using optogenetics to localize psychological functions in the nucleus accumbens (NAc), a brain region involved in the production of motivated behaviors. Together, these methods provide avenues for researchers to localize and causally demonstrate the impact of neural manipulations in the brain.

Cocaine-induced neuron subtype mitochondrial dynamics through Egr3 transcriptional regulation.

Mitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrate that cocaine affects mitochondrial dynamics and morphological characteristics within the nucleus accumbens (NAc). Further, mitochondria are differentially regulated by cocaine in dopamine receptor-1 containing medium spiny neurons (D1-MSNs) vs dopamine receptor-2 (D2)-MSNs. However, there is little understanding into cocaine-induced transcriptional mechanisms and their role in regulating mitochondrial processes. Here, we demonstrate that cocaine enhances binding of the transcription factor, early growth response factor 3 (Egr3), to nuclear genes involved in mitochondrial function and dynamics. Moreover, cocaine exposure regulates mRNA of these mitochondria-associated nuclear genes in both contingent or noncontingent cocaine administration and in both rodent models and human postmortem tissue. Interestingly, several mitochondrial nuclear genes showed distinct profiles of expression in D1-MSNs vs D2-MSNs, with cocaine exposure generally increasing mitochondrial-associated nuclear gene expression in D1-MSNs vs suppression in D2-MSNs. Further, blunting Egr3 expression in D1-MSNs blocks cocaine-enhancement of the mitochondrial-associated transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and the mitochondrial fission molecule, dynamin related protein 1 (Drp1). Finally, reduction of D1-MSN Egr3 expression attenuates cocaine-induced enhancement of small-sized mitochondria, causally demonstrating that Egr3 regulates mitochondrial morphological adaptations. Collectively, these studies demonstrate cocaine exposure impacts mitochondrial dynamics and morphology by Egr3 transcriptional regulation of mitochondria-related nuclear gene transcripts; indicating roles for these molecular mechanisms in neuronal function and plasticity occurring with cocaine exposure.

Comparison of analytical methods to determine sodium content of low-sodium foods.

U.S. nutrition labeling regulations require the declaration of sodium content on food products. Accurate and reproducible determination of Na in foods with low Na content (< 140 mg/serving) is challenging because of laboratory contamination. Within-laboratory performance of inductively coupled plasma/MS (ICP/MS), flame atomic absorption spectrophotometry (FAAS), ion-selective electrode (ISE), and potentiometric titration of chloride ion were evaluated in 17 low-sodium foods. For 13 types of food, statistically significant differences (P < 0.05) exist between the within-day andlor interday means obtained by ICP/MS, FAAS, and ISE. Median within-day and interday precent RSD values were 2.7 and 6.1, 3.5 and 3.2, and 5.6 and 6.2%, respectively, by ICP/MS, FAAS, and ISE. The fewest matrix effects were found with ICP/MS, followed by FAAS, and ISE. FAAS gave higher results in a variety of matrixes when compared to ICP/MS and/or ISE. ISE did not perform well in fatty foods or at very low Na concentrations. Manufacturers' Nutrition Facts Panel sodium declarations exceeded levels found by analysis in > 70% of the foods. Analysis of chloride content does not produce reliable Na estimates in low-sodium foods, even when added sodium chloride is present. Methodological issues and contamination sources are discussed.

Herpes Simplex Virus: Epidemiology, Diagnosis, and Treatment.

Genital herpes simplex virus infections are among the most prevalent sexually transmitted infections in the United States. It continues to be a public health concern because of its recurrent nature and potential for complications. Treatment is not curative, but rather serves to shorten the duration of symptoms and improve quality of life. Current therapies include episodic treatment and chronic suppressive therapy and are generally well tolerated and effective.

The Vanderbilt Program in Interprofessional Learning: Sustaining a Longitudinal, Clinical Experience That Aligns Practice With Education.

PROBLEM: Designing and sustaining a longitudinal, clinic-based interprofessional learning experience is logistically challenging, which has limited the educational opportunities available in health professions schools. The authors discuss the Vanderbilt Program in Interprofessional Learning (VPIL), which addresses some of the challenges facing clinic-based interprofessional experiences. APPROACH: VPIL places first- and second-year students from 4 professional degree programs (medicine, nursing, pharmacy, social work) in Nashville, Tennessee, on teams where they work and learn together in authentic clinical environments over a 2-year period. The program was implemented in 2010 and includes 3 components: a summer immersion experience, seminar-based classroom and simulation sessions, and a weekly clinical experience. Students also complete a capstone quality improvement project. VPIL administrators have set up structures at the institutional, clinic, faculty, and student levels that have contributed to the sustainability of the program. OUTCOMES: Between 2010 and 2019, VPIL admitted 398 students who participated on 91 clinical teams. In addition, 55 clinical preceptors and 12 core faculty trained students for future collaborative practice. The program has received consistently high ratings from students, who have produced 69 quality improvement projects at their clinics. These projects have addressed aspects of the care delivery process and produced durable materials, showing that the program has contributed to important innovations in the health system. NEXT STEPS: VPIL faculty continue to improve the curriculum and administrative structures and work to expand the program to reach a wider variety of health professions students. Going forward, lessons from the program could assist educators in creating opportunities for students to learn interprofessionally and deliver high value health care in increasingly complex delivery systems.

Consequences of dietary sugar consumption: A historical perspective.

The US industrial revolution led to a significant increase in the amount of dietary sugar consumed annually. The impact has become a public health crisis over the past several decades. The consequences are seen in the dramatic rise in rates of obesity, type 2 diabetes mellitus, and cardiovascular disease.

Evaluation and Treatment of Adrenal Dysfunction in the Primary Care Environment.

Adrenal insufficiency (Addison's disease) and Cushing's syndrome are rare disorders characterized by abnormal secretion of adrenal hormones. All patients with adrenal insufficiency and many with Cushing's syndrome require life-long therapy with the potential to impact the quality of life. Management requires gain of a significant amount of knowledge related to treatment, self-care, and how to react quickly in critical situations. Knowledge deficits related to management may cause patients to become critically ill and may even cause death. Ongoing patient/family teaching is crucial for proper disease management and sustaining the quality of life.

Optogenetic self-stimulation in the nucleus accumbens: D1 reward versus D2 ambivalence.

The nucleus accumbens (NAc) contains multiple subpopulations of medium spiny neurons (MSNs). One subpopulation expresses D1-type dopamine receptors, another expresses D2-type receptors, and a third expresses both. The relative roles in NAc of D1 neurons versus D2 neurons in appetitive motivation were assessed here. Specifically, we asked whether D1-Cre mice would instrumentally seek optogenetic self-stimulation specifically targeted at D1 MSNs in NAc, and similarly if D2-Cre mice would self-stimulate D2 neurons in NAc. Mice were implanted with Cre-targeted channelrhodopsin (ChR2) virus and optic fibers in NAc. Subsequently, mice could earn brief NAc laser illuminations by actively touching a metal spout in one task, or by going to a particular location in a separate task. Results indicated that D1 neuronal excitation in NAc supported intense self-stimulation in both tasks. D1-Cre mice earned hundreds to thousands of spout-touches per half-hour session, and also sought out locations that delivered NAc laser to excite D1 MSNs. By comparison, D2 ChR2 mice showed lower but still positive levels of self-stimulation in the spout-touch task, earning dozens to hundreds of NAc laser illuminations. However, in the location task, D2 mice failed to show positive self-stimulation. If anything, a few D2 individuals gradually avoided the laser location. Brain-wide measures indicated that D1 and D2 stimulations in NAc recruited heavily overlapping patterns of Fos activation in distant limbic structures. These results confirm that excitation of D1 MSNs in NAc supports strong incentive motivation to self-stimulate. They also suggest that excitation of D2 neurons in NAc supports self-stimulation under some conditions, but fails under others and possibly may even shift to negative avoidance.

Rapid sample preparation with Lyse-It® for Listeria monocytogenes and Vibrio cholerae.

Sample preparation is a leading bottleneck in rapid detection of pathogenic bacteria. Here, we use Lyse-It® for bacterial cellular lysis, genomic DNA fragmentation, and protein release and degradation for both Listeria monocytogenes and Vibrio cholerae. The concept of Lyse-It® employs a conventional microwave and Lyse-It® slides for intensely focused microwave irradiation onto the sample. High microwave power and a <60 second irradiation time allow for rapid cellular lysis and subsequent intracellular component release. The pathogenic bacteria are identified by quantitative polymerase chain reaction (qPCR), which subsequently demonstrates the viability of DNA for amplification post microwave-induced lysis. Intracellular component release, degradation, and detection of L. monocytogenes and V. cholerae has been performed and shown in this paper. These results demonstrate a rapid, low-cost, and efficient way for bacterial sample preparation on both food and water-borne Gram-positive and -negative organisms alike.

Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry.

The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH) and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc) and ventral pallidum (VP), in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact ("liking") and motivational incentive salience ("wanting") of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating vs. intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including "liking" and "wanting" for food rewards.

Analysis of organic acids in fruit juices by liquid chromatography-mass spectrometry: an enhanced tool for authenticity testing.

Organic acid analysis plays a fundamental role in the testing of authenticity of fruit juices. Analytical methods used routinely for organic acids suffer from poor reproducibility, often give false positives/negatives for tartaric acid, and do not offer the possibility of analyte confirmation. There are conflicting reports in the literature on the presence/absence of tartaric acid in pomegranate juice, a potential indicator of adulteration with grape juice. In this work, a method based on stable isotope dilution liquid chromatography-tandem mass spectrometry is described for citric, malic, quinic, and tartaric acid in fruit juices. Validation data including precision and recovery in six types of juice are presented. Tartaric and quinic acids were confirmed in pomegranate juice at concentrations of 1-5 and ∼1 mg/L, respectively. These concentrations are much lower than those resulting from adulteration with grape juice and apple juice, respectively, at the 5% level. A separate method for isocitric acid in orange juice based on the single standard addition method is also described.

Factors associated with multidrug-resistant Acinetobacter transmission: an integrative review of the literature.

Multidrug-resistant (MDR) Acinetobacter infections are occurring at alarming rates in traumatic war injuries. Causative factors have not been specifically identified. We used an integrative review of the literature guided by the Identifying, Organizing, and Synthesizing strategy to identify factors related to MDR Acinetobacter transmission. We identified five major themes of commonality relating to transmission-wound types, risk factors, contributing factors, modes of transmission, and prevention strategies-and we identified studies that should be replicated in military populations. We identified sources of transmission (ie, environment to wound, health care worker to wound) and interventions to reduce or eliminate health care-associated or surgical site MDR Acinetobacter infections (ie, using strict infection control guidelines, appropriate use of antibiotics, notification of infected patients).

Parent or caregiver, staff, and dentist perspectives on access to dental care issues for head start children in Ohio.

OBJECTIVES: We conducted 5 surveys on consumer and provider perspectives on access to dental care for Ohio Head Start children to assess the need and appropriate strategies for action. METHODS: We collected information from Head Start children (open-mouth screenings), their parents or caregivers (questionnaire and telephone interviews), Head Start staff (interviews), and dentists (questionnaire). Geocoded addresses were also analyzed. RESULTS: Twenty-eight percent of Head Start children had at least 1 decayed tooth. For the 11% of parents whose children could not get desired dental care, cost of care or lack of insurance (34%) and dental office factors (20%) were primary factors. Only 7% of general dentists and 29% of pediatric dentists reported accepting children aged 0 through 5 years of age as Medicaid recipients without limitation. Head Start staff and dentists felt that poor appointment attendance negatively affected children's receiving care, but parents/caregivers said finding accessible dentists was the major problem. CONCLUSIONS: Many Ohio Head Start children do not receive dental care. Medicaid and patient age were primary dental office limitations that are partly offset by the role Head Start plays in ensuring dental care. Dentists, Head Start staff, and parents/caregivers have different perspectives on the problem of access to dental care.

Two functional but noncomplementing Drosophila tyrosine decarboxylase genes: distinct roles for neural tyramine and octopamine in female fertility.

The trace biogenic amine tyramine is present in the nervous systems of animals ranging in complexity from nematodes to mammals. Tyramine is synthesized from tyrosine by the enzyme tyrosine decarboxylase (TDC), a member of the aromatic amino acid family, but this enzyme has not been identified in Drosophila or in higher animals. To further clarify the roles of tyramine and its metabolite octopamine, we have cloned two TDC genes from Drosophila melanogaster, dTdc1 and dTdc2. Although both gene products have TDC activity in vivo, dTdc1 is expressed nonneurally, whereas dTdc2 is expressed neurally. Flies with a mutation in dTdc2 lack neural tyramine and octopamine and are female sterile due to egg retention. Although other Drosophila mutants that lack octopamine retain eggs completely within the ovaries, dTdc2 mutants release eggs into the oviducts but are unable to deposit them. This specific sterility phenotype can be partially rescued by driving the expression of dTdc2 in a dTdc2-specific pattern, whereas driving the expression of dTdc1 in the same pattern results in a complete rescue. The disparity in rescue efficiencies between the ectopically expressed Tdc genes may reflect the differential activities of these gene products. The egg retention phenotype of the dTdc2 mutant and the phenotypes associated with ectopic dTdc expression contribute to a model in which octopamine and tyramine have distinct and separable neural activities.