Supersoft Norbornene-Based Thermoplastic Elastomers with High Strength and Upper Service Temperature.

With over 6 million tons produced annually, thermoplastic elastomers (TPEs) have become ubiquitous in modern society, due to their unique combination of elasticity, toughness, and reprocessability. Nevertheless, industrial TPEs display a tradeoff between softness and strength, along with low upper service temperatures, typically ≤100 °C. This limits their utility, such as in bio-interfacial applications where supersoft deformation is required in tandem with strength, in addition to applications that require thermal stability (e.g., encapsulation of electronics, seals/joints for aeronautics, protective clothing for firefighting, and biomedical devices that can be subjected to steam sterilization). Thus, combining softness, strength, and high thermal resistance into a single versatile TPE has remained an unmet opportunity. Through de novo design and synthesis of novel norbornene-based ABA triblock copolymers, we fill this gap. Ring-opening metathesis polymerization (ROMP) is employed to prepare TPEs with an unprecedented combination of properties, including skin-like moduli (<100 kPa), strength competitive with commercial TPEs (>5 MPa), and upper service temperatures akin to high-performance plastics (∼260 °C). Furthermore, the materials are elastic, tough, reprocessable, and shelf stable (≥2 months) without incorporation of plasticizer. Structure-property relationships identified herein inform development of next-generation TPEs that are both biologically soft yet thermomechanically durable. This article is protected by copyright. All rights reserved.

Gun violence revictimization in New York State: What increases the risk of being shot again?

BACKGROUND: While gun injuries are more likely to occur in in urban settings and affect people of color, factors associated with gun violence revictimization-suffering multiple incidents of gun violence-are unknown. We examined victim demographics and environmental factors associated with gun violence revictimization in New York state (NYS). METHODS: The 2005-2020 NYS hospital discharge database was queried for patients aged 12-65 years with firearm-related hospital encounters. Patient and environmental variables were extracted. Patient home zip code was used to determine the Social Deprivation Index (SDI) for each patient's area of residence. We conducted bivariate and multivariate analyses among patients who suffered a single incident of gun violence or gun violence revictimization. RESULTS: We identified 38,974 gun violence victims among whom 2,243 (5.8%) suffered revictimization. The proportion of revictimization rose from 4% in 2008 to 8% in 2020 (p < 0.01). The median [IQR] time from first to second incident among those who suffered revictimization was 359 [81-1,167] days. Revictimization was more common among Blacks (75.0% vs 65.1%, p < 0.01), patients with Medicaid (54.9% vs 43.2%, p < 0.01), and in areas of higher deprivation (84.8 percentile vs 82.1 percentile, p < 0.01). CONCLUSIONS: Gun violence revictimization is on the rise. People of color and those residing in areas with high social deprivation are more likely to be re-injured. Our findings emphasize the importance of community-level over individual-level interventions for prevention of gun violence revictimization. LEVEL OF EVIDENCE: Epidemiological, Level III.

Golf cart injuries have similar severity to all-terrain vehicle injuries in children: a multicenter comparison over a 5-year period.

Background: Golf carts (GCs) and all-terrain vehicles (ATVs) are popular forms of personal transport. Although ATVs are considered adventurous and dangerous, GCs are perceived to be safer. Anecdotal experience suggests increasing numbers of both GC and ATV injuries, as well as high severity of GC injuries in children. This multicenter study examined GC and ATV injuries and compared their injury patterns, resource utilization, and outcomes. Methods: Pediatric trauma centers in Florida submitted trauma registry patients age <16 years from January 2016 to June 2021. Patients with GC or ATV mechanisms were identified. Temporal trends were evaluated. Injury patterns, resource utilization, and outcomes for GCs and ATVs were compared. Intensive care unit admission and immediate surgery needs were compared using multivariable logistic regression. Results: We identified 179 GC and 496 ATV injuries from 10 trauma centers. GC and ATV injuries both increased during the study period (R2 0.4286, 0.5946, respectively). GC patients were younger (median 11 vs 12 years, p=0.003) and had more intracranial injuries (34% vs 19%, p<0.0001). Overall Injury Severity Score (5 vs 5, p=0.27), intensive care unit (ICU) admission (20% vs 16%, p=0.24), immediate surgery (11% vs 11%, p=0.96), and mortality (1.7% vs 1.4%, p=0.72) were similar for GCs and ATVs, respectively. The risk of ICU admission (OR 1.19, 95% CI 0.74 to 1.93, p=0.47) and immediate surgery (OR 1.04, 95% CI 0.58 to 1.84, p=0.90) remained similar on multivariable logistic regression. Conclusions: During the study period, GC and ATV injuries increased. Despite their innocuous perception, GCs had a similar injury burden to ATVs. Heightened safety measures for GCs should be considered. Level of evidence: III, prognostic/epidemiological.

Continuous renal replacement therapy for lithium toxicity: A worthy treatment to avoid intradialytic hypotension and vasopressors.

While intermittent hemodialysis (HD) is the most efficient method of removing lithium in patients with lithium toxicity, continuous renal replacement therapy is an acceptable alternative in the setting of intradialytic hypotension. This form of dialysis can reduce the need for vasopressors during HD, which increases mortality.

Caregiver Experiences and Burden in Moderate-Advanced Dementia With Lewy Bodies.

Background and Objectives: Dementia with Lewy bodies (DLB) is a common degenerative dementia, but research on caregiver experiences in late stages is lacking. This study aimed to investigate the caregiving experience in moderate-advanced DLB to identify opportunities for improving care and support. Methods: Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease-related measures, and measures of the caregiver experience relating to caregiver support, burden, grief, self-efficacy, depression, quality of life, and coping. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of caregiver measures with patient and caregiver variables with adjustments for multiple testing. Results: Caregivers (n = 143) were mostly women (83.5%) and spouses (84.7%) (mean age 68 years; range 37-85). Almost 40% reported high burden and/or depression. Caregiver measures correlated with fluctuation and behavioral symptom severity, sleepiness, and autonomic symptoms of the person with DLB. Higher burden correlated with worse caregiver quality of life, higher depression, and grief. Greater self-efficacy, social support, and resilience correlated with lower caregiver burden. The most frequently reported caregiver concerns were being unable to plan for the future, having to put the needs of the person with DLB ahead of the caregiver's own needs, and worry that the person with DLB would become too dependent on the caregiver, but many additional concerns were endorsed. Caregivers were generally satisfied with medical team support. The lowest reported satisfaction related to information regarding disease progression and how well medical teams shared information with each other. Discussion: Various patient-related and caregiver-related factors influence caregiver experiences in moderate-advanced DLB. Clinicians can target caregiver needs by providing support resources and DLB education and treating bothersome patient symptoms. Future research should investigate what interventions can modify and improve caregiver experiences in advanced DLB and identify therapeutics for patient symptoms currently without adequate treatments (e.g., fluctuations, daytime sleepiness). Trial Registration Information: NCT04829656.

Local gate control of Mott metal-insulator transition in a 2D metal-organic framework.

Electron-electron interactions in materials lead to exotic many-body quantum phenomena, including Mott metal-insulator transitions (MITs), magnetism, quantum spin liquids, and superconductivity. These phases depend on electronic band occupation and can be controlled via the chemical potential. Flat bands in two-dimensional (2D) and layered materials with a kagome lattice enhance electronic correlations. Although theoretically predicted, correlated-electron Mott insulating phases in monolayer 2D metal-organic frameworks (MOFs) with a kagome structure have not yet been realised experimentally. Here, we synthesise a 2D kagome MOF on a 2D insulator. Scanning tunnelling microscopy (STM) and spectroscopy reveal a MOF electronic energy gap of ∼200 meV, consistent with dynamical mean-field theory predictions of a Mott insulator. Combining template-induced (via work function variations of the substrate) and STM probe-induced gating, we locally tune the electron population of the MOF kagome bands and induce Mott MITs. These findings enable technologies based on electrostatic control of many-body quantum phases in 2D MOFs.

Distinct Escherichia coli transcriptional profiles in the guts of recurrent UTI sufferers revealed by pan-genome hybrid selection.

Low-abundance members of microbial communities are difficult to study in their native habitat. This includes Escherichia coli, a minor, but common inhabitant of the gastrointestinal tract and opportunistic pathogen, including of the urinary tract, where it causes most infections. While our understanding of the interactions between uropathogenic Escherichia coli (UPEC) and the bladder is increasing, comparatively little is known about UPEC in its pre-infection reservoir, partly due to its low abundance there (<1% relative abundance). In order to specifically and sensitively explore the genomes and transcriptomes of diverse E. coli from gastrointestinal communities, we developed E. coli PanSelect, a set of probes designed to enrich E. coli's broad pangenome. First we demonstrated the ability of PanSelect to enrich diverse strains in an unbiased way using a mock community of known composition. Then we enriched E. coli DNA and RNA from human stool microbiomes by 158 and 30-fold, respectively. We also used E. coli PanSelect to explore the gene content and transcriptome of E. coli within the gut microbiomes of women with history of recurrent urinary tract infection (rUTI), finding differential regulation of pathways that suggests that the rUTI gut environment promotes respiratory vs fermentative metabolism. E. coli PanSelect technology holds promise for investigations of native in vivo biology of diverse E. coli in the gut and other environments, where it is a minor component of the microbial community, using unbiased, culture-free shotgun sequencing. This method could also be generally applied to other highly diverse, low abundance bacteria.

Limited Sustained Remission After Nucleos(t)ide Analog Withdrawal: Results From a Large, Global, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation. METHODS: Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN. RESULTS: Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months. DISCUSSION: Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year.

Post-translational mechanisms in psychostimulant-induced neurotransmitter efflux.

The availability of monoamine neurotransmitters in the brain is under the control of dopamine, norepinephrine, and serotonin transporters expressed on the plasma membrane of monoaminergic neurons. By regulating transmitter levels these proteins mediate crucial functions including cognition, attention, and reward, and dysregulation of their activity is linked to mood and psychiatric disorders of these systems. Amphetamine-based transporter substrates stimulate non-exocytotic transmitter efflux that induces psychomotor stimulation, addiction, altered mood, hallucinations, and psychosis, thus constituting a major component of drug neurochemical and behavioral outcomes. Efflux is under the control of transporter post-translational modifications that synergize with other regulatory events, and this review will summarize our knowledge of these processes and their role in drug mechanisms.

Patient- and proxy-reported quality of life in advanced dementia with Lewy bodies.

INTRODUCTION: Little is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages. METHODS: Dyads of individuals with moderate-advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease-related measures, and measures of patient/caregiver experiences. RESULTS: The Quality of Life in Alzheimer's Disease (QoL-AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy-completed QoL-AD. Patient- and proxy-reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient-reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures. DISCUSSION: Patient- and proxy-reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB. HIGHLIGHTS: Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies. Daytime sleepiness affected patient- and proxy-reported QoL. Behavioral symptoms affected patient- and proxy-reported QoL. Autonomic symptom burden affected patient-reported QoL. Dementia severity, dependence, and caregiver experiences affected proxy ratings.

Prenatal Diagnosis of Fetal Aqueductal Stenosis: A Multicenter Prospective Observational Study through the North American Fetal Therapy Network (NAFTNet).

INTRODUCTION: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention. METHODS: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe CNS ventriculomegaly (lateral ventricle diameter >15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and MRI were calculated, as was the mean gestational age at diagnosis. RESULTS: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7w). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n=35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average. CONCLUSION: The prenatal diagnosis of fetal aqueductal stenosis can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience.

Inhibition of cellular factor TM6SF2 suppresses secretion pathways of Hepatitis B, Hepatitis C and Hepatitis D viruses.

Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all these viruses rely on secretion through the host endoplasmic reticulum-Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions and HBV subviral particles. Moreover, in a cohort of people with hepatitis B a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.

Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

Endel Tulving (1927-2023).

This article presents an obituary for Endel Tulving. Tulving's educational and professional careers are summarized. His work in the field of human memory is detailed. It is noted that Tulving's look at the field of verbal learning in the late 1950s persuaded him that the dominant associative tradition missed many important aspects of human memory. His research found that at the time of retrieval, memory for the original event may be successfully reinstated only by contextual cues that interact in a complementary fashion with the specifically encoded memory trace, a process that Tulving referred to as "synergistic ecphory". He is also known for his work on memory systems. In his book, Elements of Episodic Memory published in 1983, Tulving proposed that memory for experienced events, episodic memory, should be distinguished from general knowledge of the world, semantic memory, and from procedural memory, the learned ability to perform such skilled procedures as riding a bicycle or playing a musical instrument. He also proposed an evolutionary framework for these different but related systems, suggesting that simple animals show only procedural memory, more complex animals are consciously aware of their knowledge of the world, but only humans possess episodic memory-the ability to use "mental time travel" to consciously recreate past experiences and to imagine possible future events. Although known initially for his purely cognitive behavioral research, during the 1980s and 1990s, Tulving increasingly incorporated neuropsychological and neuroimaging approaches into his work. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Advanced Breast Cancer Guidelines in Latin America: Assessment, Adaptation, and Implementation of Fifth Advanced Breast Cancer Consensus Guidelines.

PURPOSE: As the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access. METHODS: Sixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed. RESULTS: Latin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent. CONCLUSION: Despite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias.

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.

Lessons Learned from Approval of Aducanumab for Alzheimer's Disease.

When the US Food and Drug Administration used the accelerated approval process to authorize the use of the antiamyloid drug aducanumab to treat Alzheimer's disease (AD), many people hoped this signaled a new era of disease-modifying treatment. But 2 years later, aducanumab's failure to launch provides a cautionary tale about the complexities of dementia and the need for a thorough and transparent review of the role that regulatory agencies and various stakeholders play in approving AD drugs. We highlight the events leading to aducanumab's controversial approval and discuss some of the key lessons learned from the drug's failure to deliver the hoped-for benefits. These lessons include the inherent limitations of antiamyloid strategies for a complex disease in which amyloid is only one of several pathological processes, the need for clinical trials that better reflect the diversity of communities affected by AD, the potential pitfalls of futility analyses in clinical trials, the need for greater transparency and other modifications to the approval process, and the dementia field's unreadiness to move from the highly controlled environment of clinical trials to the widespread and chronic use of resource-intensive, disease-modifying drugs in real-world treatment scenarios. People with dementia desperately need effective therapies. We hope that the aducanumab story will inspire changes to the approval process-changes that restore public trust and improve future efforts to deliver disease-modifying therapies to the clinic.

Collective overclaiming is related to collective narcissism and numeracy.

When asked to estimate how much their state or nation has contributed to history, people typically provide unreasonably large estimates, claiming that their group has contributed much more to history than nongroup members would estimate, demonstrating collective overclaiming. Why does such overclaiming occur? In the current study we examined factors that might predict collective overclaiming. Participants from 12 U.S. states estimated how much their home state contributed to U.S. history, completed measures of collective narcissism and numeracy, and rated the importance of 60 specific historical events. There was a positive relationship between collective overclaiming and collective narcissism, a negative relationship between collective overclaiming and numeracy, and a positive relationship between collective overclaiming and the importance ratings of the specific events. Together, these results indicate that overclaiming is partially and positively related to collective narcissism and negatively related to people's ability to work with numbers. We conclude that collective overclaiming is likely determined by several factors, including the availability heuristic and ego protection mechanisms, in addition to collective narcissism and relative innumeracy.

Electrophysiological correlates of attention in the locus coeruleus-prelimbic cortex circuit during the rodent continuous performance test.

Sustained attention, the ability to focus on an activity or stimulus over time, is significantly impaired in many psychiatric disorders, and there remains a major unmet need in treating impaired attention. Continuous performance tests (CPTs) were developed to measure sustained attention in humans, non-human primates, rats, and mice, and similar neural circuits are engaged across species during CPT performance, supporting their use in translational studies to identify novel therapeutics. Here, we identified electrophysiological correlates of attentional performance in a touchscreen-based rodent CPT (rCPT) in the locus coeruleus (LC) and prelimbic cortex (PrL), two inter-connected regions that are implicated in attentional processes. We used viral labeling and molecular techniques to demonstrate that neural activity is recruited in LC-PrL projections during the rCPT, and that this recruitment increases with cognitive demand. We implanted male mice with depth electrodes within the LC and PrL for local field potential (LFP) recordings during rCPT training, and identified an increase in PrL delta and theta power, and an increase in LC delta power during correct responses in the rCPT. We also found that the LC leads the PrL in theta frequencies during correct responses while the PrL leads the LC in gamma frequencies during incorrect responses. These findings may represent translational biomarkers that can be used to screen novel therapeutics for drug discovery in attention.