Investigating a bias account of emotional false memories using a criterion warning and force choice restrictions at retrieval.

Here, we add to the debate as to whether false recognition of emotional stimuli is more memory-based or more bias-based. Emotional false memory findings using the DRM paradigm have been marked by higher false alarms to negatively arousing compared to neutral critical lure items. Explanation for these findings has mainly focused on false memory-based accounts. However, here we address the question of whether a response bias for emotional stimuli can, at least in part, explain this phenomenon. In Experiment 1, we used a criterion warning, previously shown to increase more conservative responding and reduce false recognition. Experiment 2, we employed a two-alternative-forced choice test, which minimises the role of criterion setting. In both experiments, we compared false alarms to negative and neutral critical lures. We observed a significant decrease in false recognition rates for both negative and neutral critical lures under the conditions of forced choice restriction and criterion warning. However, despite these conditions, negative items, compared to their neutral counterparts, still consistently provoked a higher degree of false recognition. The discussion that follows presents an exploration of both memory-based accounts and criterion-setting explanations for the enhanced emotional false memory finding.

DCAF16-Based Covalent Handle for the Rational Design of Monovalent Degraders.

Targeted protein degradation with monovalent molecular glue degraders is a powerful therapeutic modality for eliminating disease causing proteins. However, rational design of molecular glue degraders remains challenging. In this study, we sought to identify a transplantable and linker-less covalent handle that could be appended onto the exit vector of various protein-targeting ligands to induce the degradation of their respective targets. Using the BET family inhibitor JQ1 as a testbed, we synthesized and screened a series of covalent JQ1 analogs and identified a vinylsulfonyl piperazine handle that led to the potent and selective degradation of BRD4 in cells. Through chemoproteomic profiling, we identified DCAF16 as the E3 ligase responsible for BRD4 degradation-an E3 ligase substrate receptor that has been previously covalently targeted for molecular glue-based degradation of BRD4. Interestingly, we demonstrated that this covalent handle can be transplanted across a diverse array of protein-targeting ligands spanning many different protein classes to induce the degradation of CDK4, the androgen receptor, BTK, SMARCA2/4, and BCR-ABL/c-ABL. Our study reveals a DCAF16-based covalent degradative and linker-less chemical handle that can be attached to protein-targeting ligands to induce the degradation of several different classes of protein targets.

Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Health Numeracy Is Associated With a Patient's Ability to Interpret Patient-Reported Outcome Measures Data.

BACKGROUND: Patient-reported outcome measures (PROMs) were originally developed as research tools; however, there is increasing interest in using PROMs to inform clinical care. Prior work has shown the benefits of implementing PROMs at the point of care, but a patient's health numeracy (their ability to understand and work with numbers) may affect their ability to interpret PROM results. MATERIALS AND METHODS: We recruited patients presenting to an outpatient orthopedic clinic. Forty-nine patients completed a survey that included demographic information, the short-form General Health Numeracy Test, and accuracy questions about four PROM displays (bar graph, table, line graph, pictograph) that indicated the same PROM results. RESULTS: Patients with higher health numeracy answered all display accuracy questions correctly (P=.016). Patients who preferred using the table were more likely to answer display accuracy questions incorrectly (odds ratio, 0.013, P=.024). The two most frequently preferred PROM formats were bar graphs and tables, and most patients preferred to learn about their PROM function scores via a combination of displays and verbal discussions. CONCLUSION: Patient health numeracy is associated with the ability to correctly interpret visual displays of PROMs. Implementation of PROMs at point of care currently does not account for health numeracy. Efforts to account for health numeracy when using PROMs at point of care may improve the efficacy of using PROMs to improve outcomes in orthopedic surgery. [Orthopedics. 202x;4x(x):xx-xx.].

Molecular and cellular rhythms in excitatory and inhibitory neurons in the mouse prefrontal cortex.

Previous studies have shown that there are rhythms in gene expression in the mouse prefrontal cortex (PFC); however, the contribution of different cell types and potential variation by sex has not yet been determined. Of particular interest are excitatory pyramidal cells and inhibitory parvalbumin (PV) interneurons, as interactions between these cell types are essential for regulating the excitation/inhibition balance and controlling many of the cognitive functions regulated by the PFC. In this study, we identify cell-type specific rhythms in the translatome of PV and pyramidal cells in the mouse medial PFC (mPFC) and assess diurnal rhythms in PV cell electrophysiological properties. We find that while core molecular clock genes are conserved and synchronized between cell types, pyramidal cells have nearly twice as many rhythmic transcripts as PV cells (35% vs. 18%). Rhythmic transcripts in pyramidal cells also show a high degree of overlap between sexes, both in terms of which transcripts are rhythmic and in the biological processes associated with them. Conversely, in PV cells, rhythmic transcripts from males and females are largely distinct. Moreover, we find sex-specific effects of phase on action potential properties in PV cells that are eliminated by environmental circadian disruption. Together, this study demonstrates that rhythms in gene expression and electrophysiological properties in the mouse mPFC vary both by cell type and by sex. Moreover, the biological processes associated with these rhythmic transcripts may provide insight into the unique functions of rhythms in these cells, as well as their selective vulnerabilities to circadian disruption.

Mathematical analysis of simple behavioral epidemic models.

COVID-19 highlighted the importance of considering human behavior change when modeling disease dynamics. This led to developing various models that incorporate human behavior. Our objective is to contribute to an in-depth, mathematical examination of such models. Here, we consider a simple deterministic compartmental model with endogenous incorporation of human behavior (i.e., behavioral feedback) through transmission in a classic Susceptible-Exposed-Infectious-Recovered (SEIR) structure. Despite its simplicity, the SEIR structure with behavior (SEIRb) was shown to perform well in forecasting, especially compared to more complicated models. We contrast this model with an SEIR model that excludes endogenous incorporation of behavior. Both models assume permanent immunity to COVID-19, so we also consider a modification of the models which include waning immunity (SEIRS and SEIRSb). We perform equilibria, sensitivity, and identifiability analyses on all models and examine the fidelity of the models to replicate COVID-19 data across the United States. Endogenous incorporation of behavior significantly improves a model's ability to produce realistic outbreaks. While the two endogenous models are similar with respect to identifiability and sensitivity, the SEIRSb model, with the more accurate assumption of the waning immunity, strengthens the initial SEIRb model by allowing for the existence of an endemic equilibrium, a realistic feature of COVID-19 dynamics. When fitting the model to data, we further consider the addition of simple seasonality affecting disease transmission to highlight the explanatory power of the models.

Extragenital lichen sclerosus et atrophicus-morphea overlap as an initial presentation of genital lichen sclerosus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disorder, most often characterized by atrophic skin plaques located on female genitalia. Infrequently, LSA may present extragenitally; however, much is unknown about the temporal relationship between genital and extragenital LSA. Morphea, also known as localized scleroderma, is a rare inflammatory skin condition characterized by sclerotic plaques. Investigators debate whether LSA and morphea exist on the same spectrum of disease, with LSA representing a superficial variant of morphea involving genitalia, or if they are distinct but coincidental entities. Although researchers have described LSA and morphea occurring in different locations on the same patient, few reports describe LSA and morphea occurring in the same lesion and in the inguinal folds. Herein, we report a case of a 62-year-old woman with extragenital LSA-morphea overlap in the inguinal folds, who three months later developed genital LSA. Extragenital LSA-morphea in the same plaque, with no signs of genital lesions on initial exam, with later development of genital LSA, is especially uncommon. The temporal progression of extragenital LSA-morphea overlap to genital LSA over a three-month period is an important contribution to the literature, as the temporal relationship between extragenital and genital LSA is not previously discussed.

Investigating the role of adversity and benevolence beliefs in predicting prosociality.

BACKGROUND: Does experiencing adversity engender kindness, and if so, for whom? Two studies tested the hypothesis that adversity predicts increased pro-social outcomes, and that this relationship is strongest for individuals who view others as good and trustworthy, or benevolent. METHOD: In Study 1, a cross-sectional survey design was utilized, and in Study 2 a longitudinal survey was conducted. RESULTS: In Study 1 (N = 359), the number of lifetime adverse life events was associated with increased volunteering, empathic concern, and self-reported altruism. The association of adversity and altruism was stronger for those with greater benevolence beliefs. In Study 2 (N = 1157), benevolence beliefs were assessed, and in subsequent years, adverse life events were reported. The number of past-year adverse life events predicted more volunteering and charitable involvement, but only among people with high benevolence beliefs. CONCLUSION: Exposure to adversity may be associated with increased pro-social behavior among those with higher benevolence beliefs. In part, this could be due to benevolence beliefs increasing the expectation that one's efforts will be appreciated and reciprocated.

The Importance of Networks and Relationships: Leveraging the Biocontainment Unit Leadership Workgroup for Special Pathogen Outbreak Response.

Developing and sustaining relationships and networks before an emergency occurs is crucial. The Biocontainment Unit Leadership Workgroup is a consortium of the 13 Regional Emerging Special Pathogen Treatment Centers in the United States. Established in 2017, the volunteer-based workgroup is composed of operational leaders dedicated to maintaining readiness for special pathogen care. Monthly meetings focus on addressing operational challenges, sharing best practices, and brainstorming solutions to common problems. Task forces are leveraged to tackle more complex issues that are identified as priorities. In 2022, members of the workgroup were harnessed for response efforts related to mpox, Sudan ebolavirus, and Marburg virus disease. The weekly Outbreak Readiness call is a shared effort between the Biocontainment Unit Leadership Workgroup and the Special Pathogens Research Network of the National Emerging Special Pathogens Training and Education Center. Call participants included leaders of the Regional Emerging Special Pathogen Treatment Centers and federal partners who shared weekly updates on operational readiness of units, case counts, laboratory capacity, available medical countermeasures, and other pertinent information. The routine exchange of real-time information enabled learning and collegial sharing of experiences, highlighted the experience of the network to federal partners, and provided situational awareness of special pathogen outbreaks across the country. The consortium enabled this rapid convening of partners to meet an urgent need for special pathogen response. The weekly Outbreak Readiness call is a communication model and scalable framework that serves both domestic preparedness efforts and international efforts should the need for a collaborative global response arise. In this case study, we describe the framework and experience of this partnership, along with the structure of rapid deployment for group convening.

Multisystem Involvement in a Pediatric Patient With Hypermobile Ehlers-Danlos Syndrome: A Case Report of the Diagnostic Complexity and Management Challenges.

Ehlers-Danlos syndrome (EDS) is a collection of genetic disorders caused by abnormalities in collagen and typified by hyperflexible joints, hyperextensible skin, and a tendency for easy bruising and tissue injuries. Hypermobile Ehlers-Danlos syndrome (hEDS), the most common subtype, presents a diagnostic challenge due to the lack of specific genetic markers. This case report describes a 13-year-old girl with hEDS, presenting with hypermobility, thoracolumbar scoliosis, constipation, glucosuria, microscopic hematuria, urticaria, and intermittent episodes of bilateral hand and feet swelling. Genetic testing revealed a variant of uncertain significance in the COL9A2 gene. An echocardiogram showed a mildly dilated aortic root. The complexity of her presentation underscores the challenges in diagnosing and managing hEDS with multisystem involvement.

Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort.

BACKGROUND: Pollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied. OBJECTIVE: We described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators. METHODS: Participants' geocoded addresses at enrollment (1995-1996) were linked to CWS service area boundaries and monitoring data (N = 115,206, 92%); we computed average (1990-2015) concentrations of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE). We used generalized linear regression to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption at follow-up (2017-2019) were also described. RESULTS: Medians (interquartile ranges) of average concentrations of all contaminants were below regulatory limits: arsenic: 1.03 (0.54,1.71) µg/L, uranium: 3.48 (1.01,6.18) µg/L, GA: 2.21 (1.32,3.67) pCi/L, nitrate: 0.54 (0.20,1.97) mg/L, HAA5: 8.67 (2.98,14.70) µg/L, and TTHM: 12.86 (4.58,21.95) µg/L. Among those who lived within a CWS boundary and self-reported drinking water information (2017-2019), approximately 74% self-reported their water source as municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Spatially linked water source was largely consistent with self-reported source at follow-up (2017-2019). Relative to non-Hispanic white participants, average arsenic, uranium, GA, and nitrate concentrations were higher for Black, Hispanic and Native American participants. Relative to participants living in census block groups in the lowest socioeconomic status (SES) quartile, participants in higher SES quartiles had lower arsenic/uranium/GA/nitrate, and higher HAA5/TTHM. Non-metropolitan participants had higher arsenic/uranium/nitrate, and metropolitan participants had higher HAA5/TTHM. IMPACT: Though average water contaminant levels were mostly below regulatory limits in this large cohort of California women, we observed heterogeneity in exposures across sociodemographic subgroups and neighborhood characteristics. These data will be used to support future assessments of drinking water exposures and disease risk.

The Transdiagnostic Connectome Project: a richly phenotyped open dataset for advancing the study of brain-behavior relationships in psychiatry.

An important aim in psychiatry is the establishment of valid and reliable associations linking profiles of brain functioning to clinically relevant symptoms and behaviors across patient populations. To advance progress in this area, we introduce an open dataset containing behavioral and neuroimaging data from 241 individuals aged 18 to 70, comprising 148 individuals meeting diagnostic criteria for a broad range of psychiatric illnesses and a healthy comparison group of 93 individuals. These data include high-resolution anatomical scans, multiple resting-state, and task-based functional MRI runs. Additionally, participants completed over 50 psychological and cognitive assessments. Here, we detail available behavioral data as well as raw and processed MRI derivatives. Associations between data processing and quality metrics, such as head motion, are reported. Processed data exhibit classic task activation effects and canonical functional network organization. Overall, we provide a comprehensive and analysis-ready transdiagnostic dataset, which we hope will accelerate the identification of illness-relevant features of brain functioning, enabling future discoveries in basic and clinical neuroscience.

Increasing Utilization of Scrubbing Devices for Peripheral Intravenous Disinfectable Needleless Closed Connectors.

Introduction Peripheral intravenous (IV) administration sets are a source of infection that increases morbidity, mortality, and healthcare costs. In this quality improvement project, we aimed to enhance compliance with peripheral IV hub disinfection at anesthesia induction to follow the American Society of Anesthesiologists (ASA) safe medication injection guidelines. Methods This study was conducted in the main operating suite of the University of Miami's principal hospital between June and October 2023. Audits of scrubbing device utilization by the anesthesiology team and focus groups were conducted before and after two educational interventions. Educational efforts focused on increasing compliance with peripheral IV disinfection using scrubbing devices.  Results Mean use per case, inferred from the number of devices dispensed, nearly doubled from 0.44 (95% CI, 0.37 to 0.59) to 0.82 (95% CI, 0.77 to 0.88) (P < 0.0001). Implications regarding steps to further enhance compliance are discussed. Conclusions Through a simple educational program, scrubbing device utilization increased significantly from baseline.

Femoral Head Fractures: Evaluation, Management, and Outcomes.

Fractures of the femoral head typically occur after high-energy trauma. Radiographs and cross-sectional imaging are used to appropriately classify and identify associated injuries or morphologic characteristics that may influence management. Identification of the radiographic and clinical hallmarks of an irreducible variant is critical to optimizing the patient's outcome. Nonsurgical treatment can be used in the setting of small, infrafoveal femoral head fractures without hip instability. When surgical treatment is indicated, an anterior (Smith-Petersen), posterior (Kocher-Langenbeck), or surgical hip dislocation approach may be used depending on injury details and surgeon preference. The purpose of this review was to summarize current evidence on femoral head fractures regarding indications, variant patterns, surgical approaches, and outcomes.

Building a Biocontainment Unit: Infrastructure and organizational experiences of the 13 regional biocontainment units in the United States.

The United States (US) system for special pathogen care began with a tiered structure in 2014 with the US experience treating patients with Ebola Virus Disease. Over the past decade, the federally funded US biocontainment units (BCUs), termed Regional Emerging Special Pathogen Treatment Centers (RESPTCs), have maintained operational readiness to care for patients afflicted by high-consequence infectious diseases. The RESPTC network has expanded in number of facilities and in scope, as the now 13 RESPTCs serve as regional resources for special pathogens preparedness; a role that has recently been formalized with the establishment of the National Special Pathogen System (NSPS). Lessons learned for maintaining infrastructure and operational readiness are shared with the intent of informing new and existing BCUs in the US and globally.

Repurposing FDA-approved drugs to treat chemical weapon toxicities: Interactive case studies for trainees.

The risk of a terrorist attack in the United States has created challenges on how to effectively treat toxicities that result from exposure to chemical weapons. To address this concern, the United States has organized a trans-agency initiative across academia, government, and industry to identify drugs to treat tissue injury resulting from exposure to chemical threat agents. We sought to develop and evaluate an interactive educational session that provides hands-on instruction on how to repurpose FDA-approved drugs as therapeutics to treat toxicity from exposure to chemical weapons. As part of the Rutgers Summer Undergraduate Research Fellowship program, 23 undergraduate students participated in a 2-h session that included: (1) an overview of chemical weapon toxicities, (2) a primer on pharmacology principles, and (3) an interactive session where groups of students were provided lists of FDA-approved drugs to evaluate potential mechanisms of action and suitability as countermeasures for four chemical weapon case scenarios. The interactive session culminated in a competition for the best grant "sales pitch." From this interactive training, students improved their understanding of (1) the ability of chemical weapons to cause long-term toxicities, (2) impact of route of administration and exposure scenario on drug efficacy, and (3) re-purposing FDA-approved drugs to treat disease from chemical weapon exposure. These findings demonstrated that an interactive training exercise can provide students with new insights into drug development for chemical threat agent toxicities.

Examining the feasibility and utility of heart rate variability on intervention outcomes targeting emotion regulation in autism: a brief report.

Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body's primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8-17 years who participated in the pilot study of Regulating Together, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test-retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.