Pediatric Sepsis in General Emergency Departments: Association Between Pediatric Sepsis Case Volume, Care Quality, and Outcome.

STUDY OBJECTIVE: To assess whether a general emergency department's (ED) annual pediatric sepsis volume increases the odds of delivering care concordant with Surviving Sepsis pediatric guidelines. METHODS: A retrospective cohort study of children <18 years with sepsis presenting to 29 general EDs. Emergency department and hospital data were abstracted from the medical records of 2 large health care systems, including all hospitals to which children were transferred. Guideline-concordant care was defined as intravenous antibiotics within 3 hours, intravenous fluid bolus within 3 hours, and lactate measured. The association between annual ED pediatric sepsis encounters and the probability of receiving guideline-concordant care was assessed. RESULTS: We included 1,527 ED encounters between January 1, 2015, and September 30, 2021. Three hundred and one (19%) occurred in 25 EDs with <10 pediatric sepsis encounters annually, 466 (31%) in 3 EDs with 11 to 100 pediatric sepsis encounters annually, and 760 (50%) in an ED with more than 100 pediatric sepsis encounters annually. Care was concordant in 627 (41.1%) encounters. In multivariable analysis, annual pediatric sepsis volume was minimally associated with the probability of guideline-concordant care (odds ratio 1.002 [95% confidence interval 1.001 to 1.00]). Care concordance increased from 23.1% in 2015 to 52.8% in 2021. CONCLUSION: Guideline-concordant sepsis care was delivered in 41% of pediatric sepsis cases in general EDs, and annual ED pediatric sepsis encounters had minimal association with the odds of concordant care. Care concordance improved over time. This study suggests that factors other than pediatric sepsis volume are important in driving care quality and identifying drivers of improvement is important for children first treated in general EDs.

Routine Emergency Department Screening to Decrease Subsequent Physical Abuse.

STUDY OBJECTIVE: Emergency department (ED) screening for child physical abuse has been widely implemented, with uncertain effects on child abuse identification. Our goal was to determine the effect of screening on referrals to child protective services (CPS) identifying abuse. METHODS: We performed a retrospective cohort study of children younger than 6 years old with an ED encounter at 1 of 2 large health care systems, one of which implemented routine child abuse screening. The main outcome was initial (<2 days) or subsequent (3 to 180 days) referral to CPS identifying child abuse using linked records. We compared outcomes for the 2-year period after screening was implemented to the preperiod and nonscreening EDs using generalized estimating equations to adjust for sex, age, race/ethnicity, payor and prior ED encounters and clustered by center. RESULTS: Of the 331,120 ED encounters, 41,589 (12.6%) occurred at screening EDs during the screening period. Screening was completed in 34,272 (82%) and was positive in 188 (0.45%). Overall, 7,623 encounters (2.3%) had a subsequent referral, of which 589 (0.2%) identified moderate or severe abuse. ED screening did not change initial (adjusted odds ratio [aOR]=1.01, 95% confidence interval [CI] 0.89 to 1.15) or subsequent referral to CPS when compared to the prescreening period (aOR=1.05, 95% CI 0.9 to 1.18) or to the nonscreening EDs (aOR=1.06, 95% CI 0.92 to 1.21). CONCLUSION: Routine screening did not affect initial or subsequent referrals to CPS.

Nonfatal Emergency Department Visits Associated with Fall-Related Fractured Skulls of Infants Aged 0-4 Months.

BACKGROUND: Children aged 0-4 years have the highest rate of emergency department (ED) visits for traumatic brain injury (TBI); falls are the leading cause. Infants younger than 2 years are more likely to sustain a fractured skull after a fall. OBJECTIVE: This study examined caregiver actions and products associated with ED visits for fall-related fractured skulls in infants aged 0-4 months. METHODS: Data were analyzed from the 2001-2017 National Electronic Injury Surveillance System-All Injury Program. Case narratives of infants aged 0-4 months who visited an ED for a fall-related skull fracture were examined to code caregiver actions preceding the fall. Product codes determined fall location and product type involved (e.g., flooring, bed, or stairs). All national estimates were weighted. RESULTS: There were more than 27,000 ED visits (weighted estimate) of infants aged 0-4 months for a nonfatal fall-related fractured skull between 2001 and 2017. Most were younger than 2 months (46.7%) and male (54.4%). Falls occurred primarily in the home (69.9%) and required hospitalization (76.4%). Primary caregiver actions coded involved placing (58.6%), dropping (22.7%), and carrying an infant (16.6%). Floor surfaces were the most common product (mentioned in 24.0% of the cases). CONCLUSIONS: Fall-related fractured skulls are a health and developmental concern for infants, highlighting the importance of a comprehensive assessment at the time of the injury to better understand adult actions. Findings indicated the need to develop prevention messages that include safe carrying and placement of infants.

Effect of Routine Child Physical Abuse Screening Tool on Emergency Department Efficiency.

OBJECTIVES: Physical abuse is a significant cause of morbidity and mortality for children. Routine screening by emergency nurses has been proposed to improve recognition, but the effect on emergency department (ED) workflow has not yet been assessed. We sought to evaluate the feasibility of routine screening and its effect on length of stay in a network of general EDs. METHODS: A 2-question child physical abuse screening tool was deployed for children <6 years old who presented for care in a system of 27 general EDs. Data were compared for the 6 months before and after screening was deployed (4/1/2019-10/2/2019 vs 10/3/2019-3/31/2020). The main outcome was ED length of stay in minutes. RESULTS: There were 14,133 eligible visits in the prescreening period and 16,993 in the screening period. Screening was completed for 13,404 visits (78.9%), with 116 (0.7%) screening positive. The mean ED length of stay was not significantly different in the prescreening (95.9 minutes) and screening periods (95.2 minutes; difference, 0.7 minutes; 95% CI, -1.5, 2.8). Among those who screened positive, 29% were reported to child protective services. On multivariable analysis, implementation of the screening tool did not impact overall ED length of stay. There were no significant differences in resource utilization between the prescreening and screening periods. CONCLUSIONS: Routine screening identifies children at high risk of physical abuse without increasing ED length of stay or resource utilization. Next steps will include determining rates of subsequent serious physical abuse in children with or without routine screening.

Examining ethical issues that arise in providing ED/hospital care for patients experiencing elder mistreatment and approaches to address them.

Clinicians in the emergency department and hospital who treat patients experiencing elder mistreatment (EM) can expect to encounter challenging ethical dilemmas. Collaboration with ethics and EM consultation services offers teams an important opportunity to improve patient-centered outcomes and address value-based concerns when treating these patients. This article describes the role of a hospital clinical ethics consultation service and best practices for collaboration between ethics and EM consultation services. Illuminated via four case studies, the article presents several core ethical frameworks, including allowing patients the dignity of risk, considerations around a harm reduced discharge, involving abusers in surrogate decision making, and providers' experience of moral distress when dealing with patients experiencing EM. Increasing collaboration with ethics and elder mistreatment services can help teams more effectively respond to EM.

ED/hospital program contributions to community multi-disciplinary team meetings: Different models.

Elder mistreatment (EM) is a complex problem, with response and prevention requiring contributions from professionals from many disciplines. Community-based multi-disciplinary teams (MDTs) that conduct meetings to discuss challenging cases and coordinate services are a common strategy to ensure effective collaboration. Though they play an important role in EM identification, intervention, and prevention, hospitals and hospital-based healthcare professionals have been particularly difficult to engage in MDTs. Two hospitals in different communities recently launched Emergency Department (ED)/hospital-based response teams to consult in cases of potential EM, and both participate in MDTs. We explored similarities and differences between the MDTs in these communities including in the role of the ED/hospital-based response team. The comparison demonstrates both core common features as well as large variations. These differences reflect different circumstances in the models on which they were based, on MDT development in these communities, available resources and infrastructure, and the ED/hospital program's role.

Elder abuse geriatrics: describing an important new medical specialist.

Elder mistreatment, including elder abuse and neglect, is a difficult diagnosis to make and manage for most providers. To address this, two elder abuse consultation teams were developed for patients in the hospital and emergency department settings. As these teams have developed, the providers involved have obtained specialized training and experience that we believe contributes to a new field of elder abuse geriatrics, a corollary to the well-established field of child abuse pediatrics. Providers working in this field require specialized training and have a specialized scope of practice that includes forensic evaluation, evaluation of cognition and capacity, care coordination and advocacy for victims of abuse, and collaboration with protective services and law enforcement. Here we describe the training, scope of practice, ethical role, and best practices for elder mistreatment medical consultation. We hope this will serve as a starting point for this new and important medical specialty.

Evaluation of Children after Caregiver Intimate Partner Violence: A Qualitative Study of Barriers, Facilitators, and Trauma- and Violence-Informed Care.

OBJECTIVE: To identify barriers and facilitators of evaluating children exposed to caregiver intimate partner violence (IPV) and develop a strategy to optimize the evaluation. STUDY DESIGN: Using the EPIS (Exploration, Preparation, Implementation, and Sustainment) framework, we conducted qualitative interviews of 49 stakeholders, including emergency department clinicians (n = 18), child abuse pediatricians (n = 15), child protective services staff (n = 12), and caregivers who experienced IPV (n = 4), and reviewed meeting minutes of a family violence community advisory board (CAB). Researchers coded and analyzed interviews and CAB minutes using the constant comparative method of grounded theory. Codes were expanded and revised until a final structure emerged. RESULTS: Four themes emerged: (1) benefits of evaluation, including the opportunity to assess children for physical abuse and to engage caregivers; (2) barriers, including limited evidence about the risk of abuse in these children, burdening a resource-limited system, and the complexity of IPV; (3) facilitators, including collaboration between medical and IPV providers; and (4) recommendations for trauma- and violence-informed care (TVIC) in which a child's evaluation is leveraged to link caregivers with an IPV advocate to address the caregiver's needs. CONCLUSIONS: Routine evaluation of IPV-exposed children may lead to the detection of physical abuse and linkage to services for the child and the caregiver. Collaboration, improved data on the risk of child physical abuse in the context of IPV and implementation of TVIC may improve outcomes for families experiencing IPV.

Prevalence of cerebral sinovenous thrombosis in abusive head trauma.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) has been proposed in legal settings to be an atraumatic mimic of abusive head trauma (AHT). OBJECTIVE: The objective of this study was to determine the prevalence of CSVT and subdural hemorrhage (SDH) in a large AHT population. MATERIALS AND METHODS: This retrospective cohort study measured the prevalence of CSVT and SDH on magnetic resonance venograms in 243 patients diagnosed with AHT at a single center. We also reported additional intra- and extracranial injuries, head injury severity and length of hospital stay. RESULTS: Among 243 patients diagnosed with AHT, 7% (16/243) had CSVT. SDH was present in 94% (15/16) of the CSVT cases. Cytotoxic edema and subarachnoid hemorrhage were in 88% (14/16) and 69% (11/16) of the CSVT cases, respectively. Extracranial signs of abuse were also in 100% (16/16) of the patients with CSVT. Critical to maximal head injury severity (abbreviated injury scale >=5) was in 75% (12/16) of the CSVT population vs. 33% (82/243) in the total AHT population. Length of hospital and pediatric intensive care unit stay was greater in those with CSVT (10 vs. 21.9 and 3.5 vs. 7.3 days). CONCLUSION: These findings suggest that CSVT is uncommon in AHT and is associated with additional traumatic injuries and greater injury severity.

"These Are Our Kids": Qualitative Interviews With Clinical Leaders in General Emergency Departments on Motivations, Processes, and Guidelines in Pediatric Sepsis Care.

STUDY OBJECTIVE: Sepsis is a leading cause of pediatric death requiring emergency resuscitation. Most children with sepsis are treated in general emergency departments (EDs); however, research has focused on pediatric EDs. We sought to identify barriers and facilitators to pediatric sepsis care in general EDs, including care processes, the role of guidelines, and incentivized metrics. METHODS: In this qualitative study, we conducted semistructured interviews with key informant physician and nurse leaders overseeing pediatric sepsis in general EDs in 2021, including medical directors, nurse managers, and quality coordinators. Interviews were audio-recorded, transcribed, and coded using deductive domains based on steps of sepsis care, pediatric readiness, and structural dynamics. Domains were analyzed across interviews in matrices, using thematic analysis within domains. RESULTS: Twenty-one clinical leaders representing 26 hospitals, including trauma levels I to IV, were interviewed. The themes included the following: (1) motivation to improve pediatric sepsis care based on moral imperative and location; (2) need for actionable pediatric sepsis guidelines; (3) children's hospitals' role in education, protocols, transfer, and consultation; and (4) mixed feelings about reportable metrics, particularly in EDs with low pediatric volume. Sepsis care process challenges included diagnosis, intravenous access, and antibiotic delivery but varied among hospitals. CONCLUSION: Leaders in general EDs were motivated to provide high-quality pediatric sepsis care but disagreed on whether reportable metrics would drive improvements. They universally sought direct support from their nearest children's hospitals and actionable guidelines. Efforts to address pediatric sepsis quality in general EDs should prioritize guideline design, responsive pediatric transfer and consultation systems, and locally specific process improvement.

Injuries Suggestive of Physical Abuse in Young Children With Subconjunctival Hemorrhages.

OBJECTIVE: The aim of this study was to compare the demographic characteristics, clinical presentations, medical evaluation, and injuries identified in a cohort of children with and without subconjunctival hemorrhage who were evaluated by a child abuse specialist. METHODS: This was a case-control study that used data from the ExSTRA (Examining Siblings to Recognize Abuse) research network. Subjects with a subconjunctival hemorrhage(s) were designated as cases. Four controls matched for age and participating center were included for each case. Descriptive statistics were used to compare cases and controls. RESULTS: Fifty of the 2890 subjects in the parent study had a subconjunctival hemorrhage(s) and were designated as cases. The cases had a median (interquartile range) age of 5.0 months (2.0-23.6 months). Two hundred controls were matched to the cases. There was no difference in the demographics, clinical characteristics, medical evaluation, or rate of occult injuries identified in cases and controls. Almost one-quarter of children with subconjunctival hemorrhages had no other external sign of trauma but had the same rate of occult injuries as children with bruises. CONCLUSIONS: These data suggest that subconjunctival hemorrhages are relatively rare among children undergoing evaluation by a child abuse specialist, but that they are often an indicator of occult injury. Even in the absence of other external signs of trauma, the presence of subconjunctival hemorrhages should prompt an age-appropriate evaluation for physical abuse.

Cervical Spine Imaging and Injuries in Young Children With Non-Motor Vehicle Crash-Associated Traumatic Brain Injury.

OBJECTIVES: The aim of this study was to evaluate cervical magnetic resonance imaging (MRI) and computed tomography (CT) practices and cervical spine injuries among young children with non-motor vehicle crash (MVC)-associated traumatic brain injury (TBI). METHODS: We performed a retrospective study of a stratified, systematic random sample of 328 children younger than 2 years with non-MVC-associated TBI at 4 urban children's hospitals from 2008 to 2012. We defined TBI etiology as accidental, indeterminate, or abuse. We reported the proportion, by etiology, who underwent cervical MRI or CT, and had cervical abnormalities identified. RESULTS: Of children with non-MVC-associated TBI, 39.4% had abusive head trauma (AHT), 52.2% had accidental TBI, and in 8.4% the etiology was indeterminate. Advanced cervical imaging (CT and/or MRI) was obtained in 19.1% of all children with TBI, with 9.3% undergoing MRI and 11.7% undergoing CT. Cervical MRI or CT was performed in 30.9% of children with AHT, in 11.7% of accidental TBI, and in 10.7% of indeterminate-cause TBI. Among children imaged by MRI or CT, abnormal cervical findings were found in 22.1%, including 31.3% of children with AHT, 7.1% of children with accidental TBI, and 0% of children with indeterminate-cause TBI. Children with more severe head injuries who underwent cervical imaging were more likely to have cervical injuries. CONCLUSIONS: Abusive head trauma victims appear to be at increased risk of cervical injuries. Prospective studies are needed to define the risk of cervical injury in children with TBI concerning for AHT and to inform development of imaging guidelines.

Thermodynamic Modeling of Calcium Sulfate Hydrates in a CaSO4-H2SO4-H2O System from 273.15 to 473.15 K up to 5 m Sulfuric Acid.

To prevent scaling and to recycle aqueous solutions in industrial processes, the thermodynamic properties of the CaSO4-H2SO4-H2O system are studied by thermodynamic modeling with the Pitzer model. The published solubility data of calcium sulfate hydrates in sulfuric acid solutions were collected and reviewed critically. Then, the CaSO4-H2SO4-H2O system was modeled using the Pitzer activity coefficient approach from critically selected experimental data to obtain optimized parameters. The model reproduces the solubility data with good accuracy up to 5 m sulfuric acid at temperatures of 283.15-368.15, 283.15-473.15, and 298.15-398.15 K for gypsum (CaSO4·2H2O), anhydrite (CaSO4), and hemihydrate (CaSO4·0.5H2O), respectively. However, at temperatures above 398.15 K and sulfuric acid concentration above 0.5 mol/kg, the solubility of anhydrite predicted by our model deviates significantly from the literature data. Our model predicts that the solubility of anhydrite would first increase but then decrease in more concentrated sulfuric acid solutions, which is in disagreement with the experimental data showing constantly increasing solubilities as a function of increasing sulfuric acid concentration. This discrepancy has been discussed. The transformations of gypsum to anhydrite and hemihydrate were predicted in sulfuric acid solutions. With increasing H2SO4 concentration, the transformation temperatures of gypsum to anhydrite and hemihydrate will decrease. Thus, gypsum is stable at low temperatures in solutions of low H2SO4 concentrations and transforms to anhydrite at high temperatures and in concentrated H2SO4 solutions, while hemihydrate is always a metastable phase. Furthermore, the predicted results were compared with previous experimental studies to verify the accuracy of the model.

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte-Neuron Lactate Shuttle in the Brain.

BACKGROUND: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones. METHODS: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs. RESULTS: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs. CONCLUSION: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.

Thermodynamic Modeling of Calcium Sulfate Hydrates in the CaSO4-H2O System from 273.15 to 473.15 K with Extension to 548.15 K.

Calcium sulfate is one of the most common inorganic salts with a high scaling potential. The solubility of calcium sulfate was modeled with the Pitzer equation at a temperature range from 273.15 to 473.15 K from published solubility data, which was critically evaluated. Only two Pitzer parameters, ß(1) and ß(2), with simple temperature dependency are required to model the solubility with excellent extrapolating capabilities up to 548.15 K. The stable temperature range for gypsum is 273.15-315.95 K, whereas above 315.95 K the stable phase is anhydrite. Hemihydrate is in the metastable phase in the whole temperature range, and the obtained metastable invariant temperature from gypsum to hemihydrate is 374.55 K. The obtained enthalpy and entropy changes at 298.15 K for the solubility reactions are in good agreement with literature values yielding solubility products of 2.40 × 10-05, 3.22 × 10-05, and 8.75 × 10-05 for gypsum, anhydrite, and hemihydrate, respectively. The obtained Pitzer model for the CaSO4-H2O system is capable of predicting the independent activity and osmotic coefficient data with experimental accuracy. The mean absolute average error of activity coefficient data at 298.15 K is less than 2.2%. Our model predicts the osmotic coefficient on the ice curve within 1.5% maximum error.

Use of Imaging in Children With Witnessed Physical Abuse.

OBJECTIVE: Physicians are occasionally asked to evaluate children who are reported to have been victims of witnessed abuse, but who have no injuries noted on examination. The rate of injury in these patients is presently unknown. This is important because abuse allegations are brought for both altruistic and other reasons. This study compares the use of skeletal survey and neuroimaging in well-appearing and clearly injured children reported to be victims of witnessed child abuse. METHODS: Retrospectively planned secondary analysis of the Examination of Siblings to Recognize Abuse cohort of children referred to a child abuse pediatrician with concerns for physical abuse. Children were selected who presented to a medical provider with a history of witnessed child abuse including shaking. Rates of radiographically evident injuries are noted among children with and without injuries noted on physical examination. RESULTS: Among 2890 children evaluated by a child abuse pediatrician, 90 children (3.1%) presented with a history of witnessed abuse. Among these, 51 children (57%) had injuries noted on physical examination; 9 (29%) of 31 skeletal surveys and 9 (35%) of 26 neuroimaging studies revealed injuries. Of 39 children (43%) with witnessed abuse and normal examination, 3 (10%) of 30 skeletal surveys and 2 (8%) of 25 neuroimaging studies revealed an injury. CONCLUSIONS: A significant minority of children evaluated for allegations of witnessed abuse will have occult injuries identified radiographically. Absence of injury on examination should not deter physicians from obtaining otherwise indicated skeletal surveys and neuroimaging in children reported to have experienced witnessed abuse.

Occult head injury is common in children with concern for physical abuse.

BACKGROUND: Studies evaluating small patient cohorts have found a high, but variable, rate of occult head injury in children <2 years old with concern for physical abuse. The American College of Radiology (ACR) recommends clinicians have a low threshold to obtain neuroimaging in these patients. OBJECTIVES: Our aim was to determine the prevalence of occult head injury in a large patient cohort with suspected physical abuse using similar selection criteria from previous studies. Additionally, we evaluated proposed risk factors for associations with occult head injury. MATERIALS AND METHODS: This was a retrospective, secondary analysis of data collected by an observational study of 20 U.S. child abuse teams that evaluated children who underwent subspecialty evaluation for concern of abuse. We evaluated children <2 years old and excluded those with abnormal mental status, bulging fontanelle, seizure, respiratory arrest, underlying neurological condition, focal neurological deficit or scalp injury. RESULTS: One thousand one hundred forty-three subjects met inclusion criteria and 62.5% (714) underwent neuroimaging with either head computed tomography or magnetic resonance imaging. We found an occult head injury prevalence of 19.7% (141). Subjects with emesis (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-6.8), macrocephaly (OR 8.5, 95% CI 3.7-20.2), and loss of consciousness (OR 5.1, 95% CI 1.2-22.9) had higher odds of occult head injury. CONCLUSION: Our results show a high prevalence of occult head injury in patients <2 years old with suspected physical abuse. Our data support the ACR recommendation that clinicians should have a low threshold to perform neuroimaging in patients <2 years of age.

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter.

The neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1-/-) in mice. Here we perform quantitative LC-MS/MS neuroproteomics in the dHip and NAc of ENT1-/- mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling and protein expression patterns suggesting deficits in glutamate degradation, GABAergic signaling, as well as significant changes in bioenergetics and energy homeostasis (oxidative phosphorylation, TCA cycle, and glycolysis). These pathways are consistent with previously reported behavioral and biochemical phenotypes that typify mice lacking ENT1. Moreover, we validated decreased expression of the SNARE complex protein VAMP1 (synaptobrevin-1) in the dHip as well as decreased expression of pro-dynorphin (PDYN), neuroendocrine convertase (PCSK1), and Leu-Enkephalin (dynorphin-A) in the NAc. Taken together, our proteomic approach provides novel pathways indicating that ENT1-regulated signaling is essential for neurotransmitter release and neuropeptide processing, both of which underlie learning and reward-seeking behaviors.