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Objective Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis. Methods We present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent. Results Sequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS. Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive. Interpretation The diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS is a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting.

The ability of young children to manage their emotions and behaviors and to make meaningful friendships is an important prerequisite for school readiness and academic success. Socially competent children are also more academically successful and poor social skills are a strong predictor of academic failure. This article describes The Incredible Years Dinosaur Social Skills and Problem-Solving Child Training Program, which teaches skills such as emotional literacy, empathy or perspective taking, friendship and communication skills, anger management, interpersonal problem solving, and how to be successful at school. The program was first evaluated as a small group treatment program for young children who were diagnosed with oppositional defiant and conduct disorders. More recently the program has been adapted for use by preschool and elementary teachers as a prevention curriculum designed to increase the social, emotional, and academic competence, and decrease problem behaviors of all children in the classroom. The content, methods, and teaching processes of this classroom curriculum are discussed. [ABSTRACT FROM AUTHOR]

Background: The call for quality improvement and patient safety (QI/PS) education has increased at every level of medical education. Here, the authors present a QI/PS experiential platform implemented at the University of Florida College of Medicine (UFCOM). The project established a peer-taught hands-on learning platform in a student-run clinic allowing participants to learn and apply QI/PS concepts and tools in a real-world clinic environment. The aims were to assess students' perceptions in regard to (1) student confidence in quality improvement (QI) methodology, and (2) competency in executing QI initiatives in healthcare as measured by a post-participation survey., Method: A medical student-led quality improvement team was embedded within University of Florida's (UF's) existing student-run clinic network. The QI/PS student-team collaborated with clinic leaders and utilized QI/PS tools to establish, monitor, and expand impactful Plan-Do-Study-Act (PDSA) cycles. The impact of the training was then evaluated using The New World Kirkpatrick Model leveraging a post-project survey which included the Beliefs, Attitudes, Skills, and Confidence in Quality Improvement (BASiC-QI) survey and questions on overall student perceptions., Results: This project demonstrated positive results in all four levels of Kirkpatrick evaluation: (1) Reaction, (2) Learning, (3) Behavior, and (4) Results. This was shown through (1) a voluntary feedback survey that reported positive feedback from participants with 93% of respondents indicating they "strongly agreed" or "agreed" to positive perception questions; (2) significantly higher scores (p < 0.001) on the BASiC-QI Scale for project participants vs. non-participants; (3) the completion of 4.25 PDSA cycles per QI team; and (4) a 10.1% reduction in median patient time in clinic., Conclusions: This study supports the utility of incorporating a student-led QI/PS interactive platform into student-run clinics to increase knowledge and attitude in implementing QI/PS endeavors while simultaneously improving clinic metrics and outcomes for patients., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose of the Study: Psilocybin is a rapidly-emerging treatment for depression, yet its impact on sleep is not well understood. We sought to explore the literature on sleep and psilocybin use, and explore the topic using our own primary data., Findings: Whilst clinical trials demonstrate large depressive symptom improvements, the impact of psilocybin on sleep quality or insomnia symptoms, has not been directly studied. Using our own preliminary-data we demonstrated that both depressive-symptoms and sleep-disturbances decreased significantly following psilocybin use, though sleep improvements were smaller compared to depressive symptoms. More severe sleep-disturbances at baseline were linked to lower probability of depression remission, underscoring a potential interaction between sleep and psilocybin's efficacy. Addressing sleep disturbances could enhance therapeutic outcomes in psilocybin-assisted therapy and could lead to more effective, personalized treatment-strategies. Future research should focus on populations with sleep disorders, and on examining causal-pathways of sleep physiology's impact on psilocybin efficacy., Competing Interests: Declarations. Author Disclosures: MJR has a patent for a machine-learning-based sleep-EEG neuromodulation device with intended applications in precision medicine. Since 2018, He has also received financial and non-financial support from Oura Health Ltd, Whoop Inc, and Big-health Ltd, and has received honoraria from the British Medical Journal publishing for acting as an Associate Editor. RCH is a scientific advisor to TRYP therapeutics, Journey Collab’, Osmind, MindState, Entheos Labs, Otsuka. Competing Interests: MJR has a patent for a machine-learning-based sleep-EEG neuromodulation device with intended applications in precision medicine. Since 2018, He has also received financial and non-financial support from Oura Health Ltd, Whoop Inc, and Big-health Ltd, and has received honoraria from the British Medical Journal publishing for acting as an Associate Editor. RCH is a scientific advisor to TRYP therapeutics, Journey Collab’, Osmind, MindState, Entheos Labs, Otsuka., (© 2024. The Author(s).)

Microdeletions at the 22q11.2 locus are associated with increased risk for schizophrenia. Recent work has demonstrated that antipsychotic naïve 22q11.2 carriers display elevated levels of dopamine synthesis capacity (DSC) as assessed by 18 F-DOPA PET imaging. While this is consistent with a role for abnormal dopamine function in schizophrenia, it is unclear what molecular changes may be associated with this neuro-imaging endophenotype, and moreover, if these alterations occur independently of clinical presentation. We therefore conducted a pilot study in which we generated human induced pluripotent stem cells (hiPSCs) from two 22q11.2 deletion carriers with elevated DSC in vivo, but distinct clinical presentations. From these and neurotypical control lines we were able to robustly generate midbrain dopaminergic neurons (mDA-neurons). We then assessed whether genes associated with dopamine synthesis, metabolism or signaling show altered expression between genotypes and further between the 22q11.2 deletion lines. Our data showed alterations in expression of genes associated with dopamine metabolism and signaling that differed between the two 22q11.2 hiPSC lines with distinct clinical presentations. This reinforces the importance of considering clinical, genetic and molecular information, when possible, when choosing which donors to generate hiPSCs from, to carry out mechanistic studies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs., Methods: The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed., Perspectives: This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions., Competing Interests: M.J.R. has a patent pending for a sleep neural network-based sleep-stage classifier with intended applications to wireless sleep-EEG devices. None of the other authors have conflicts of interests.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Background: The University of Florida (UF) Equal Access Clinic Network (EACN) is the largest student-run free healthcare clinic network in Florida. The UF EACN serves those who are underinsured or uninsured in Alachua County and its surrounding area. Nationally, average total clinic time per medical visit has been established to be 84 min., Problem: Before this project, average patient cycle time at the UF EACN was 125.3 min, and there was no established quality improvement (QI) team to implement changes to address inefficiencies., Methods: This was a prospective QI study that recorded patient cycle times for patients who received healthcare at any of the four primary care free clinics across the UF EACN from 5 July 2022 to 6 April 2023., Interventions: Eighteen Plan-Do-Study-Act cycles were tailored to each of the four primary care clinic's needs with a focus on reducing patient cycle time by addressing the following identified problems: prolonged intake process, translation services, limited numbers of volunteers, and other inefficiencies and bottlenecks in workflow., Results: The median patient cycle time at the EACN shifted from 125.3 min to 112.7 min over a nine month period. This drop of 12.6 min meant patients saw a 10.1% reduction in patient cycle time across the EACN., Conclusion: Underserved patients at EACN are experiencing increased value by having shorter patient cycle times., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The University of Florida Equal Access Clinic Network (EACN) is the largest student-run free clinic (SRFC) network in Florida. This student-driven, continuous quality improvement (CQI) project is intended to decrease total patient visit length at Eastside clinic, one of EACN's primary care sites. The original median visit length of 126.25 minutes represented a significant time burden for patients, especially those with limited transportation or inflexible schedules., Methods: Over six months, four Plan-Do-Study-Act (PDSA) cycles were implemented. PDSA cycle 1 increased personnel and space for taking vitals. PDSA cycle 2 reduced redundancy in the intake process. PDSA cycle 3 triaged patients to match patient complexity with student experience level. PDSA cycle 4 introduced "nudge" interventions to reinforce clinic flow. Total patient visit length and time spent at each step of clinic flow were recorded anonymously for each patient visit. The median visit length per week was tracked on a run chart., Results: From PDSA cycle 1 through PDSA cycle 4, the median visit length decreased from 126 minutes to 114 minutes. This shift was primarily driven by a decrease in the length of patient intake from a median of 19 minutes to 9 minutes. The run chart did not show clear trends until PDSA cycle 4, which demonstrated a strong downward trend., Conclusion: This study demonstrated the ability of a student-driven CQI model to decrease patient visit length in an SRFC setting. Similar models could be used to address this and other contributors to patient experience across SRFCs nationwide., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. University of Florida Health Sebastian Ferrero Office of Clinical Quality and Patient Safety issued approval 2295. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Reid et al.)

Objective: Patients with chronic pain disorders, including Temporomandibular Disorders (TMDs) endorse high levels of sleep disturbances, frequently reporting reduced sleep quality. Despite this, little is known about the effect that daytime pain has on the microstructure and macro-architecture of sleep. Therefore, we aimed to examine the extent to which daytime pain sensitivity, measured using quantitative sensory testing (QST), is associated with objective sleep parameters the following night, including sleep architecture and power spectral density, in women with TMD., Methods: 144 females with myalgia and arthralgia by examination using the Diagnostic criteria for TMD completed a comprehensive QST battery consisting of General Pain Sensitivity, Central Sensitization Index, and Masseter Pressure Pain Threshold assessments. Polysomnography was collected the same night to measure sleep architecture and calculate relative power in delta, theta, alpha, sigma, and beta power bands., Results: Central Sensitization (B = -3.069, P = .009), General Pain Sensitivity Indices (B = -3.069, P = .007), and Masseter Pain Pressure Threshold (B = 0.030, P = .008) were significantly associated with lower REM% both before and after controlling for covariates. Pain sensitivity measures were not significantly associated with relative power in any of the spectral bands nor with any other sleep architectural stages., Conclusions: Our findings demonstrate that higher generalized pain sensitivity, masseter pain pressure threshold, as well as central sensitization were associated with a lower percentage of REM in participants with myofascial pain and arthralgia of the masticatory system. These findings provide an important step toward understanding the mechanistic underpinnings of how chronic pain interacts with sleep physiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms., Methods: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models were used to explore: (1) main and interactive effects of drug group, and time on sleep-EEG band power, and (2) associations between sleep-EEG band power change, depressive symptoms, and withdrawal severity., Results: Oscillatory spectral power tended to be greater in the suvorexant groups. Over the course of the study, decreases in delta power were observed in all study groups (β = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg: β = 2.579, d = 0.413, p = 0.009 | 40 mg β = 5.265, d = 0.847, p < 0.001) alpha power (20 mg: β = 158.304, d = 0.397, p = 0.009 | 40 mg: β = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg: β = 48.97, d = 0.410, p < 0.001 | 40 mg: β = 71.54, d = 0.568, p < 0.001) were observed in the two suvorexant groups. During the four-night taper, decreases in delta power were associated with decreases in depressive symptoms (20 mg: β = 190.90, d = 0.308, p = 0.99 | 40 mg: β = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg: β = 215.55, d = 0.034, p = 0.006 | 40 mg: β = 192.64, d = -0.854, p = <0.001), in both suvorexant groups and increases in sigma power were associated with decreases in withdrawal severity (20 mg: β = -357.84, d = -0.659, p = 0.004 | 40 mg: β = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg: β = 740.58, d = 0.964 p = <0.001 | 40 mg: β = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only: β = 335.54, d = 0.560, p = 0.023) were associated with reduced depressive symptoms in the placebo group., Conclusions: Results highlight a complex and nuanced relationship between sleep-EEG power and symptoms of depression and withdrawal. Changes in delta power may represent a mechanism influencing depressive symptoms and withdrawal., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Poor sleep is common in inflammatory bowel disease (IBD) and may be associated with overall worse disease outcomes. While the sleep/IBD literature is growing, the data are often self-reported. Further, much of the research using objective measures of sleep architecture, or the overall pattern of sleep depth, rely on single-night assessments, which can be of questionable validity., Design: Participants with IBD and healthy controls were recruited from Dartmouth-Hitchcock Medical Center as part of a two-phase clinical trial. Sleep architecture was assessed using three nights of in-home electroencephalographic monitoring and scored according to the American Academy of Sleep Medicine guidelines., Results: Our sample included 15 participants with IBD and 8 healthy controls. Participants with IBD were more psychiatrically complex, with more self-reported insomnia, anxiety and depression. Participants with IBD evidenced greater microarousals than healthy controls. In participants with IBD, microarousals were associated with lower insomnia and greater depression scores. Within IBD, participants with clinically significant insomnia evidenced trend towards lower sleep efficiency, while self-reported disease activity did not significantly impact findings., Conclusions: The methodology of past research may have impacted findings, including the reliance on single-night assessments and limited generalisability. Future research that uses robust, multinight assessments of sleep architecture in large, diverse samples is clearly warranted, as is research exploring the impact of cognitive and behavioural factors on sleep architecture and arousal., Trial Registration Number: NCT04132024., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The European and U.S. chemical agencies have listed approximately 800k chemicals about which knowledge of potential risks to human health and the environment is lacking. Filling these data gaps experimentally is impossible, so in silico approaches and prediction are essential. Many existing models are however limited by assumptions (e.g., linearity and continuity) and small training sets. In this study, we present a supervised direct classification model that connects molecular descriptors to toxicity. Categories can be driven by either data (using k -means clustering) or defined by regulation. This was tested via 907 experimentally defined 96 h LC 50 values for acute fish toxicity. Our classification model explained ≈90% of the variance in our data for the training set and ≈80% for the test set. This strategy gave a 5-fold decrease in the frequency of incorrect categorization compared to a quantitative structure-activity relationship (QSAR) regression model. Our model was subsequently employed to predict the toxicity categories of ≈32k chemicals. A comparison between the model-based applicability domain (AD) and the training set AD was performed, suggesting that the training set-based AD is a more adequate way to avoid extrapolation when using such models. The better performance of our direct classification model compared to that of QSAR methods makes this approach a viable tool for assessing the hazards and risks of chemicals.

Introduction: Patients with chronic pain experience a high prevalence of comorbid insomnia, which is associated with functional impairment. Recent advances in sleep electroencephalography (sleep-EEG) may clarify the mechanisms that link sleep and chronic pain. In this clinical update, we outline current advancements in sleep-EEG assessments for pain and provide research recommendations., Results: Promising preliminary work suggests that sleep-EEG spectral bands, particularly beta, gamma, alpha, and delta power, may create candidate neurophysiological signatures of pain, and macro-architectural parameters (e.g., total sleep time, arousals, and sleep continuity) may facilitate EEG-derived sleep phenotyping and may enable future stratification in the treatment of pain., Conclusion: Integration of measures obtained through sleep-EEG represent feasible and scalable approaches that could be adopted in the future. We provide research recommendations to progress the field towards a deeper understanding of their utility and potential future applications in clinical practice., Competing Interests: M.J.R. received nonfinancial support from Oura Health Ltd and Whoop, Inc. and Big Health ltd. M.J.R also has a patent pending for an automated sleep decoding system. M.Q. is a consultant for Natus. P.H.F. is on the Scientific Advisory Board of Ninnion Therapeutics.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Ketamine is an effective antidepressant, but there is substantial variability in patient response and the precise mechanism of action is unclear. Neuroimaging can provide predictive and mechanistic insights, but findings are limited by small sample sizes. This systematic review covers neuroimaging studies investigating baseline (pre-treatment) and longitudinal (post-treatment) biomarkers of responses to ketamine. All modalities were included. We performed searches of five electronic databases (from inception to April 26, 2022). 69 studies were included (with 1751 participants). There was substantial methodological heterogeneity and no well replicated biomarker. However, we found convergence across some significant results, particularly in longitudinal biomarkers. Response to ketamine was associated with post-treatment increases in gamma power in frontoparietal regions in electrophysiological studies, post-treatment increases in functional connectivity within the prefrontal cortex, and post-treatment increases in the functional activation of the striatum. Although a well replicated neuroimaging biomarker of ketamine response was not identified, there are biomarkers that warrant further investigation., Competing Interests: Declaration of interests GSS conducted an investigator-initiated study that used medication (vortioxetine) provided without charge by Lundbeck. TDG is listed as coauthor on patent and patent applications related to the pharmacology and use of (2R,6R)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the University of Maryland, Baltimore, but will share a percentage of any royalties that might be received. TDG has also received research funding from Allergan and Roche Pharmaceuticals. CAZ is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the US Government but will share a percentage of any royalties that might be received. FSB is a scientific adviser for WavePaths, and MindState Design Labs. FSG has received research grant support from Janssen Therapeutics. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

HIV represents a significant health burden in the United States. In 2012, the Centers for Disease Control and Prevention (CDC) stopped recommending many once-promoted interventions as part of a shift from one HIV intervention policy, Diffusion of Effective Behavioral Interventions (DEBI), to another, High Impact Prevention (HIP). Twenty-nine staff members from 10 organizations were interviewed to explore how organizations reacted to this shift. Three major themes emerged: (1) Personal experience, community assessment, and epidemiological evidence influenced organizations' perceptions of efficacy and preference for earlier interventions. (2) Organizations were concerned that HIP interventions were not a good fit for their priority populations. (3) Organizations were frustrated with the top-down approach by the CDC prioritizing HIP interventions over earlier interventions. These results indicate that organizations continue to see value in and provide DEBI interventions. In addition, a more participatory process incorporating qualitative evidence and organizations' experiences may be necessary to achieve widespread de-implementation of DEBI interventions.

Chronic pain is prevalent in older adults. Treatment, especially with opioids, is often ineffective and poses considerable negative consequences in this population. To improve treatment, it is important to understand why older adults are at a heightened risk for developing chronic pain. Insomnia is a major modifiable risk factor for chronic pain that is ubiquitous among older adults. Insomnia can also lead to heightened systemic inflammation and affective disturbance, both of which may further exacerbate pain conditions in older adults. Endotoxin exposure can be used as an experimental model of systemic inflammation and affective disturbance. The current study aims to understand how insomnia status and endotoxin-induced changes in inflammation and affect (increased negative affect and decreased positive affect) may interact to impact pain facilitatory and inhibitory processes in older adults. Longitudinal data will also assess how pain processing, affective, and inflammatory responses to endotoxin may predict the development of pain and/or depressive symptoms. The current study is a randomized, double-blinded, placebo-controlled, mechanistic clinical trial in men and women, with and without insomnia, aged 50 years and older. Participants were randomized to either 0.8ng/kg endotoxin injection or saline placebo injection. Daily diaries were used to collect variables related to sleep, mood, and pain at two-week intervals during baseline and 3-, 6-, 9-, and 12-months post-injection. Primary outcomes during the experimental phase include conditioned pain modulation, temporal summation, and affective pain modulation ∼5.5 hours after injection. Primary outcomes for longitudinal assessments are self-reported pain intensity and depressive symptoms. The current study uses endotoxin as an experimental model for pain. In doing so, it aims to extend the current literature by: (1) including older adults, (2) investigating insomnia as a potential risk factor for chronic pain, (3) evaluating the role of endotoxin-induced affective disturbances on pain sensitivity, and (4) assessing sex differences in endotoxin-induced hyperalgesia., Clinicaltrialsgov: NCT03256760., Trial Sponsor: NIH R01AG057750-01., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Astrocytes are key homeostatic and defensive cells of the central nervous system (CNS). They undertake numerous functions during development and in adulthood to support and protect the brain through finely regulated communication with other cellular elements of the nervous tissue. In Alzheimer's disease (AD), astrocytes undergo heterogeneous morphological, molecular and functional alterations represented by reactive remodelling, asthenia and loss of function. Reactive astrocytes closely associate with amyloid β (Aβ) plaques and neurofibrillary tangles in advanced AD. The specific contribution of astrocytes to AD could potentially evolve along the disease process and includes alterations in their signalling, interactions with pathological protein aggregates, metabolic and synaptic impairments. In this review, we focus on the purinergic receptor, P2X7R, and discuss the evidence that P2X7R activation contributes to altered astrocyte functions in AD. Expression of P2X7R is increased in AD brain relative to non-demented controls, and animal studies have shown that P2X7R antagonism improves cognitive and synaptic impairments in models of amyloidosis and tauopathy. While P2X7R activation can induce inflammatory signalling pathways, particularly in microglia, we focus here specifically on the contributions of astrocytic P2X7R to synaptic changes and protein aggregate clearance in AD, highlighting cell-specific roles of this purinoceptor activation that could be targeted to slow disease progression., (© 2023 The Author(s).)

Existing data demonstrate reduced delta power during sleep in patients with depression and chronic pain. However, there has been little examination of the relationship between delta power and pain-reports, or pain-catastrophizing. We recruited female participants (n = 111) with insomnia and temporomandibular disorder, and measured nocturnal and daytime measures of pain and pain catastrophizing, and calculated relative nocturnal delta (0.5-4 Hz) power during sleep. We fit linear regression models, and further examined the moderating effect of depressive symptom severity. Lower relative delta power across the whole night was significantly associated with greater nocturnal pain (B = -20.276, P = .025, R 2  = 0.214). Lower relative delta power during the first-third of the night, was associated with greater nocturnal pain (B = -17.807, p = 0.019, R 2  = 0.217), next-day pain (B = 13.876, P = .039, R 2  = 0.195), and next-morning pain (B = -15.751, P = .022, R 2  = 0.198). Lower relative delta power during the final-third of the night was significantly associated with greater nocturnal (B = -17.602, P = .029, R 2  = 0.207) and next-morning pain (3 rd : B = -14.943, P = .042, R 2  = 0.187). Depressive symptom severity did not moderate these relationships. Delta power was not significantly associated with nocturnal or daytime pain catastrophizing. These findings demonstrate that greater relative delta power during sleep is associated with lower nocturnal and next-day pain in patients with temporomandibular disorder. This data may guide the use of sleep interventions in clinical pain populations, with the aim of improving pain outcomes. PERSPECTIVE: This article presents data demonstrating an association between increased nocturnal delta power and reduced next-day pain. These findings may help promote interventions which aim to increase nocturnal delta power in clinical pain populations, with the goal of improving pain outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Previous research shows that experimental sleep deprivation alters emotion processing, suggesting a potential mechanism linking sleep disruption to mental ill-health. Extending previous work, we experimentally disrupted sleep continuity in good sleepers and assessed next-day emotion processing and regulation using tasks with established sensitivity to depression. In a laboratory-based study, 51 good sleepers (37 female; mean [SD] age 24 [3.63] years), were randomised to 1 night of uninterrupted sleep (n = 24) or sleep continuity disruption (n = 27). We assessed emotion perception, attention, and memory the following day. Participants also completed an emotion regulation task and measures of self-reported affect, anxiety, sleepiness, overnight declarative memory consolidation, and psychomotor vigilance. Confirming the effects of the manipulation, sleep continuity disruption led to a marked decrease in polysomnography-defined total sleep time (229.98 versus 434.57 min), increased wake-time after sleep onset (260.66 versus 23.84 min), and increased sleepiness (d = 0.81). Sleep continuity disruption led to increased anxiety (d = 0.68), decreased positive affect (d = -0.62), reduced overnight declarative memory consolidation (d = -1.08), and reduced psychomotor vigilance (longer reaction times [d = 0.64] and more lapses [d = 0.74]), relative to control. However, contrary to our hypotheses, experimental sleep disruption had no effect on perception of, or bias for, emotional facial expressions, emotional memory for words, or emotion regulation following worry induction. In conclusion, 1 night of sleep continuity disruption had no appreciable effect on objective measures of emotion processing or emotion regulation in response to worry induction, despite clear effects on memory consolidation, vigilance, and self-reported affect and anxiety., (© 2022 European Sleep Research Society.)

Adverse childhood experiences (ACEs) have been associated with worse sleep, but existing literature is limited by use of predominantly White samples, lack of objective sleep measurement, and use of non-standardized questionnaires. We investigated associations between retrospectively reported ACEs and sleep in adulthood in a sample of 43 adults 20-53 years of age, free from chronic conditions, with a Body mass index (BMI) ≥ 25 (Mean age = 33.14 [SD = 10.05], 74% female, 54% Black). Sleep efficiency (SE), total sleep time (TST), wake after sleep onset (WASO), and sleep onset latency (SOL), were measured by actigraphy and daily diary. Global sleep quality and insomnia severity were measured by questionnaires. Sleepiness, fatigue, and sleep quality were also measured by daily diary. Adjusting for demographic characteristics and BMI, ACEs were significantly associated with poorer global sleep quality and diary measures of greater daytime sleepiness, fatigue, and poorer sleep quality. There were no significant associations between ACEs and SE, TST, WASO, or SOL measured by diary or actigraphy. Findings suggest that ACEs are associated with worse sleep perception and daytime functioning in adulthood. Larger prospective studies are needed to replicate these findings, examine racial/ethnic differences, and determine temporal associations between ACEs, sleep, and health (e.g., BMI)., (© 2022 John Wiley & Sons Ltd.)

Populations at high risk for COVID-19- including Spanish speakers-may face additional barriers to obtaining COVID-19 vaccinations; by understanding their challenges, we can create more equitable vaccine interventions. In this study, we used interviews to identify barriers and enablers to COVID-19 vaccine uptake among participants in the San Francisco Department of Public Health contact tracing program. Data analysis employed Capability, Opportunity, Motivation Behavior model (COM-B) and the Behavior Change Wheel framework as guides to target barriers with interventions and supporting policies. This paper presents data from interviews focused on COVID-19 vaccine uptake that was part of a project to improve COVID-19 preventive behaviors in San Francisco. We completed seventeen interviews between February and May 2021; six (35%) were completed in English and 11 (65%) in Spanish. Barriers to vaccine uptake included an unprepared health system, fear of side effects, limited knowledge, and conflicting information. Behavioral factors influencing vaccine uptake were mainly related to physical opportunity, automatic motivation, and psychological capability. Interventions that could address the most significant number of barriers included education, enablement, and environmental restructuring. Finally, communication and marketing policies that use diverse multi-lingual social media and environmental planning that includes accessible vaccine sites for people with disabilities, literacy barriers, and limited English proficiency could significantly increase vaccination. Public health departments should tailor interventions to high-risk populations by understanding the specific barriers they face. This exploratory study suggests how implementation science can provide frameworks to achieve this., Competing Interests: Conflict of interestNone of the authors have any financial or non-financial interest related to this work to disclose., (© The Author(s) 2023.)

Sleep disturbance predicts worse pain outcomes. Because sleep disturbance inequitably impacts Black adults - with racism as the upstream cause - understanding how racism-related stress impacts pain through sleep might help minimize racialized pain inequities. This preliminary study examined sequential mediation of the effect of racism-related stress on experimental pain through sleep disturbance and corticolimbic μOR function in pain-free non-Hispanic Black (NHB) and White (NHW) adults. Participants completed questionnaires, actigraphy, positron emission tomography, and sensory testing. We reproduced findings showing greater sleep disturbance and pain sensitivity among NHB participants; greater sleep disturbance (r = .35) and lower pain tolerance (r=-.37) were significantly associated with greater racism-related stress. In a sequential mediation model, the total effect of racism-related stress on pain tolerance (β=-.38, P = .005) weakened after adding sleep disturbance and ventromedial prefrontal cortex (vmPFC) μOR binding potential (BP ND ) as mediators (β = -.18, P = .16). The indirect effect was statistically significant [point estimate = -.003, (-.007, -.0003). Findings showed a potential sequentially mediated effect of racism-related stress on pain sensitivity through sleep disturbance and vmPFC μOR BP ND. As policy efforts are enacted to eliminate the upstream cause of systemic racism, these results cautiously suggest that sleep interventions within racism-based trauma informed therapy might help prevent downstream effects on pain. PERSPECTIVE: This preliminary study identified the effect of racism-related stress on pain through sleep disturbance and mu-opioid receptor binding potential in the ventromedial prefrontal cortex. Findings cautiously support the application of sleep interventions within racism-based trauma-informed therapy to prevent pain inequities as policy changes function to eliminate all levels of racism., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

According to estimates put forward in multiple studies, tire and road wear particles are one of the largest sources to microplastic contamination in the environment. There are large uncertainties associated with local emissions and transport of tire and road wear particles into environmental compartments, highlighting an urgent need to provide more data on inventories and fluxes of these particles. To our knowledge, the present paper is the first published data on mass concentrations and snow mass load of tire and polymer-modified road wear particles in snow. Roadside snow and meltwater from three different types of roads (peri-urban, urban highway and urban) were analysed by Pyrolysis Gas Chromatography Mass Spectrometry. Tire particle mass concentrations in snow (76.0-14,500 mg/L meltwater), and snow mass loads (222-109,000 mg/m 2 ) varied widely. The concentration ranges of polymer-modified particles were 14.8-9550 mg/L and 50.0-28,800 mg/m 2 in snow and meltwater, respectively. Comparing the levels of tire and PMB particles to the total mass of particles, showed that tire and PMB-particles combined only contribute to 5.7% (meltwater) and 5.2% (mass load) of the total mass concentration of particles. The large variation between sites in the study was investigated using redundancy analysis of the possible explanatory variables. Contradictory to previous road studies, speed limit was found to be one of the most important variables explaining the variation in mass concentrations, and not Annual Average Daily Traffic. All identified variables explained 69% and 66%, for meltwater and mass load concentrations, respectively. The results show that roadside snow contain total suspended solids in concentrations far exceeding release limits of tunnel and road runoff, as well as tire particles in concentrations comparable to levels previously reported to cause toxicity effects in organisms. These findings strongly indicate that roadside snow should be treated before release into the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Tire and road wear particles may constitute the largest source of microplastic particles into the environment. Quantification of these particles are associated with large uncertainties which are in part due to inadequate analytical methods. New methodology is presented in this work to improve the analysis of tire and road wear particles using pyrolysis gas chromatography mass spectrometry. Pyrolysis gas chromatography mass spectrometry of styrene butadiene styrene, a component of polymer-modified bitumen used on road asphalt, produces pyrolysis products identical to those of styrene butadiene rubber and butadiene rubber, which are used in tires. The proposed method uses multiple marker compounds to measure the combined mass of these rubbers in samples and includes an improved step of calculating the amount of tire and road based on the measured rubber content and site-specific traffic data. The method provides good recoveries of 83-92% for a simple matrix (tire) and 88-104% for a complex matrix (road sediment). The validated method was applied to urban snow, road-side soil and gully-pot sediment samples. Concentrations of tire particles in these samples ranged from 0.1 to 17.7 mg/mL (snow) to 0.6-68.3 mg/g (soil/sediment). The concentration of polymer-modified bitumen ranged from 0.03 to 0.42 mg/mL (snow) to 1.3-18.1 mg/g (soil/sediment)., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Centroiding is one of the major approaches used for size reduction of the data generated by high-resolution mass spectrometry. During centroiding, performed either during acquisition or as a pre-processing step, the mass profiles are represented by a single value (i.e., the centroid). While being effective in reducing the data size, centroiding also reduces the level of information density present in the mass peak profile. Moreover, each step of the centroiding process and their consequences on the final results may not be completely clear. Here, we present Cent2Prof, a package containing two algorithms that enables the conversion of the centroided data to mass peak profile data and vice versa. The centroiding algorithm uses the resolution-based mass peak width parameter as the first guess and self-adjusts to fit the data. In addition to the m / z values, the centroiding algorithm also generates the measured mass peak widths at half-height, which can be used during the feature detection and identification. The mass peak profile prediction algorithm employs a random-forest model for the prediction of mass peak widths, which is consequently used for mass profile reconstruction. The centroiding results were compared to the outputs of the MZmine-implemented centroiding algorithm. Our algorithm resulted in rates of false detection ≤5% while the MZmine algorithm resulted in 30% rate of false positive and 3% rate of false negative. The error in profile prediction was ≤56% independent of the mass, ionization mode, and intensity, which was 6 times more accurate than the resolution-based estimated values.

Objective This study aimed to identify the types and frequency of acute medical events at a university with a collegiate-based emergency medical services (CBEMS) agency. Participants: Patients who requested assistance from the studied CBEMS agency, which provides emergency medical services coverage at a medium-sized urban university. Methods: This retrospective chart review examined requests for emergency service from August 2010-July 2017. Data abstracted include the type of medical event, frequency, call times/dates, and locations of reported medical events. Results: The studied agency received an average 889.4 (SD +/-68.6 calls) per year with the most common falling under the categories of "Substance Abuse" (231.7 calls/year, SD +/-15.7) and "Minor Trauma" (207.1 calls/year, SD+/-37.8). Most requests for acute medical attention occurred between the hours of 1800-0600 on Fridays and Saturdays. Implications/Conclusions: These results suggest that universities can potentially predict patterns and prepare for the types of acute medical issues that occur on campus.

Growing evidence suggests that public health organizations continue to provide inefficient interventions even when better intervention options may be available. Factors informing an organization's decision to continue providing inefficient interventions are unclear. We present an analysis of HIV service organizations to understand factors influencing organizations to continue or end interventions. Between 2017 and 2019, HIV service organizations were recruited from the Center for Disease Control and Prevention's (CDC) website gettested.org, in the 20 metropolitan areas with the highest HIV incidence. Organizations were eligible to participate if they had provided at least one of 37 HIV prevention interventions identified as inefficient by the CDC. 877 organizations were recruited, with a response rate of 66%, (n = 578). Thirty-eight percent (n = 213) of organizations met the eligibility criteria, and 188 organizations completed the survey asking about reasons for continuing or ending interventions. Funding status (41%, n = 79) and client demand for interventions (60%, n = 116) were reported as the primary driving factors why organizations continued ineffective interventions. Scientific evidence was a rarely reported reason for ending an inefficient intervention (12%, n = 23). Qualitative responses indicated interventions were continued if clients demanded interventions they found useful or if staff perceived interventions as improving client behavior and health outcomes. Conversely, interventions were ended if client demand or retention was low, not relevant to the target population or funding ended. The decision to continue or end inefficient interventions is influenced by a number of factors-most often by funding and client interest but not scientific evidence., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A 33-year-old woman on chronic immunosuppressive treatment for rheumatoid arthritis with a history of inhaled methamphetamine use presented with respiratory failure requiring mechanical ventilation for a prolonged period. After being given plasma exchange, pulses of methylprednisolone and a dose of cyclosporine for suspected ANCA (anti-neutrophilic cytoplasmic autoantibodies) vasculitis, she developed an obstructive supraglottic laryngeal mass that required a tracheostomy to bypass. Biopsy findings revealed the mass to be an inflammatory pseudomass secondary to cytomegalovirus (CMV). The mass resolved after several weeks of intravenous ganciclovir therapy. This is an extremely unusual presentation of localised CMV disease, with only two or three similar cases having been reported worldwide.

Introduction and Importance: Gastric mucormycosis is a rare condition that usually manifests in immunocompromised patients. It's a lethal disease with a poor prognosis requiring prompt diagnosis and aggressive management. Although found more commonly in immunocompromised patients, it can also affect the immunocompetent patient, highlighting the importance of clinical suspicion when dealing with a critically ill patient., Case Presentation: This is a case report on a patient who presented with penetrating trauma to the abdomen requiring surgical intervention. Damage control surgery was performed in the form of a right hemicolectomy ('clip and drop') for extensive colonic injuries (AAST Grade V) with contamination of the abdominal cavity [1]. In the days subsequent to the injury, he developed sepsis and progressive bowel ischaemia and necrosis, requiring surgical debridement. Histological findings revealed mucormycosis of the gastrointestinal tract., Clinical Discussion: The diagnosis of mucormycosis depends on high clinical suspicion as well as histopathological evidence. The management comprises of surgical debridement and appropriate antifungal therapy. Timeous diagnosis and adequate treatment may improve the prognosis., Conclusion: This was a challenging case for the clinicians involved, highlighting that the clinician should consider this infection as a rare cause of bowel ischaemia in the back of their minds when dealing with such patients., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Since the discovery of the C9orf72 repeat expansion mutation as causative for chromosome 9-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in 2011, a multitude of cellular pathways have been implicated. However, evidence has also been accumulating for a key mechanism of cellular compartmentalization-phase separation. Liquid-liquid phase separation (LLPS) is fundamental for the formation of membraneless organelles including stress granules, the nucleolus, Cajal bodies, nuclear speckles and the central channel of the nuclear pore. Evidence has now accumulated showing that the formation and function of these membraneless organelles is impaired by both the toxic arginine rich dipeptide repeat proteins (DPRs), translated from the C9orf72 repeat RNA transcript, and the repeat RNA itself. Both the arginine rich DPRs and repeat RNA themselves undergo phase separation and disrupt the physiological phase separation of proteins involved in the formation of these liquid-like organelles. Hence abnormal phase separation may explain a number of pathological cellular phenomena associated with C9orf72 -ALS/FTD. In this review article, we will discuss the principles of phase separation, phase separation of the DPRs and repeat RNA themselves and how they perturb LLPS associated with membraneless organelles and the functional consequences of this. We will then discuss how phase separation may impact the major pathological feature of C9orf72 -ALS/FTD, TDP-43 proteinopathy, and how LLPS may be targeted therapeutically in disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Solomon, Smikle, Reid and Mizielinska.)

The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ultimately produce. We used radio astrometry to refine the distance to the black hole x-ray binary Cygnus X-1, which we found to be [Formula: see text] kiloparsecs. When combined with archival optical data, this implies a black hole mass of 21.2 ± 2.2 solar masses, which is higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system (within the Milky Way) constrains wind mass loss from massive stars., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)