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The histone variant H2A.Z plays a critical role in chromatin-based processes such as transcription, replication, and repair in eukaryotes. Although many H2A.Z-associated processes and features are conserved in plants and animals, a distinguishing feature of plant chromatin is the enrichment of H2A.Z in the bodies of genes that exhibit dynamic expression, particularly in response to differentiation and the environment. Recent work sheds new light on the plant machinery that enables dynamic changes in H2A.Z enrichment and identifies additional chromatin-based pathways that contribute to transcriptional properties of H2A.Z-enriched chromatin. In particular, analysis of a variety of responsive loci reveals a repressive role for H2A.Z in expression of responsive genes and identifies roles for SWR1 and INO80 chromatin remodelers in enabling dynamic regulation of H2A.Z levels and transcription. These studies lay the groundwork for understanding how this ancient histone variant is harnessed by plants to enable responsive and dynamic gene expression (Graphical Abstract).

Ketamine is an anesthetic drug that has recently been approved for the treatment of treatment-resistant depression. Females are diagnosed with Major Depressive Disorder at higher rates than males, yet most of the pre-clinical research on ketamine has been conducted in male subjects. The literature on the acute and long-term behavioral and cognitive effects of ketamine shows conflicting results. It is important to examine the acute and long-term cognitive and behavioral effects of ketamine exposure at lower sub-anesthetic doses, as the recreational use of the drug at higher doses is associated with cognitive and memory impairments. The current study examined the effects of acute and repeated ketamine exposure on anxiety-like behavior, novel object recognition memory, depression-like behavior, and plasma corticosterone levels in adult female C57BL/6J mice. Mice were exposed acutely or repeatedly for 10 consecutive days to saline or 15 mg/kg ketamine and behavior was measured in the open field test, novel object recognition test, and the Porsolt forced swim test. Plasma corticosterone levels were measured following behavioral testing. Acute ketamine exposure decreased locomotor activity and increased anxiety-like behavior in the open field test compared to controls, while repeated ketamine exposure impaired memory in the novel object recognition test. There were no effects of acute or repeated ketamine exposure on depression-like behavior in the Porsolt forced swim test or on plasma corticosterone levels. These findings suggest that a subanesthetic dose of ketamine alters behavior and cognition in female mice and the effects are dependent on the duration of exposure.

This work presents a strongly-coupled fluid–structure interaction (FSI) formulation for compressible flows that is developed based on an augmented Lagrangian approach. The method is suitable for handling problems that involve nonmatching fluid–structure interface discretizations. In this work, the fluid is modeled using a stabilized finite element method for the Navier–Stokes equations of compressible flows and is coupled to the structure, which is formulated using isogeometric Kirchhoff–Love shells. The strongly-coupled system is solved using a block-iterative approach. The proposed method is validated using two compressible flow benchmark problems to assess the accuracy of the developed formulation.

BACKGROUND AND OBJECTIVES: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as “ictal-interictal-injury continuum” (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns. METHODS: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes. RESULTS: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and “other” classes, SPaRCNet exceeds the following percentages of 20 experts—ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively. DISCUSSION: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.

Objective:To compare specific life stressors and domestic abuse that pregnant women with epilepsy (WWE) experience compared to pregnant women without epilepsy (WWoE).Methods:The Pregnancy Risk Assessment Monitoring System (PRAMS) is an annual weighted survey of randomly sampled postpartum women administered by the Centers for Disease Control (CDC). We used data from PRAMS from 2012-2020 in 13 states to assess the life stressors reported by WWE compared to WWoE. We adjusted the data for maternal age, race, ethnicity, marital status, education, and socioeconomic status (SES; using income, WIC, and Medicaid use). We also examined reported abuse in WWE compared to WWoE.Results:This study included data from 64,951 postpartum women, representing 4,072,189 women through weighted sampling. Of these, 1,140 reported having a diagnosis of epilepsy in the 3 months prior to their pregnancies (representing 81,021 WWE). WWE experienced a higher number of stressors compared to WWoE. WWE were more likely to have experienced 9 out of the 14 stressors asked in the PRAMS questionnaire: severe illness of a close family member, separation or divorce, homelessness, loss of a partner’s job, cut in work hours or pay, arguing more than usual with their partner, serving jail time, substance abuse problem in a close contact, and death of a close contact. After adjusting for demographics (age, race, and SES), epilepsy was still associated with a higher number of stressors in pregnant women. Other factors associated with stressors were younger age, Indigenous or mixed race, non-Hispanic ethnicity, lower income, and WIC or Medicaid use. Those who were married were less likely to report stressors. WWE were also more likely to report abuse before or during their pregnancies.Conclusions:While managing stress is important in both epilepsy and pregnancy, WWE experience more stressors than do WWoE. After adjusting for maternal age, race, and SES, this increase in stressors persisted. Women who were younger, with lower income, on WIC or Medicaid, or not married also were more likely to experience life stressors. Alarmingly, reported abuse was also higher in WWE compared to WWoE. Attention from clinicians and support services for WWE is needed to optimize good pregnancy outcomes.

To describe the process of peer-delivered Whole Health Coaching, a primary care-based intervention in which peers provide patients with individualized support to set and work toward wellness goals. Fifteen primary care Veterans with PTSD participated in peer-delivered Whole Health Coaching during a multiple baseline design study. This is a planned mixed methods concurrent equal status analysis of the process of peer-delivered Whole Health Coaching including patient engagement, patient experience, fidelity to the coaching and peer roles, and patient satisfaction. Data sources were feedback interviews, electronic medical record reviews, self-report assessments, and observer fidelity ratings of session recordings. Qualitative data were used to expand the interpretation of quantitative descriptive data. A rapid assessment approach was used for qualitative analysis. Retention in peer-delivered Whole Health Coaching was 11 of 15 participants, and factors facilitating engagement were peers as providers and flexibility in scheduling/modality of sessions. Peers demonstrated high fidelity to coaching skills, Whole Health Coaching phases and stages, and the peer role. Participants expressed high satisfaction and perceived peer-delivered Whole Health Coaching as helpful with making progress on individualized wellness goals. Results build on the literature describing the expansion of peer services into primary care and implementation of interventions such as wellness coaching. This initial small study suggests that peers can deliver high-quality wellness coaching, and this description of the process can guide the integration of peers doing wellness coaching in similar clinical settings and for future research trials. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perioperative venous thromboembolism (VTE) is a significant cause of morbidity and mortality after gynecologic cancer surgery. Here we report a quality improvement intervention to increase perioperative VTE chemoprophylaxis compliance.All operations performed by a gynecologic oncologist at a tertiary urban university medical center admitted to the hospital for at least one midnight were included. Using a pre/post design with a washout period, we sought to increase perioperative VTE chemoprophylaxis compliance from 22% in the historical control (HC) cohort to 90% in the quality improvement (QI) cohort. The perioperative VTE chemoprophylaxis process was standardized by addressing four domains: preoperative VTE chemoprophylaxis, surgical time-out, postoperative VTE chemoprophylaxis, and intervention education and compliance tracking. Pearson's chi-square test was used to compare HC vs QI cohort compliance.There were 130 surgical cases in the HC cohort and 131 in the QI cohort. Forty-two percent underwent laparotomy, and 57% had cancer at the time of operation. VTE chemoprophylaxis compliance improved from 22% in the HC cohort to 82% in the QI cohort (p0.001). Preoperative VTE chemoprophylaxis compliance improved from 76% in the HC cohort to 94% in the QI cohort (p0.001), and postoperative VTE chemoprophylaxis compliance improved from 27% to 87% (p0.001). Thirty-day postoperative VTE occurred in three patients (2%) in the HC cohort and none in the QI cohort (p = 0.08).A low-cost and low-technology QI initiative intervention improved perioperative compliance with VTE chemoprophylaxis.

Background Perinatal Mood and Anxiety Disorders and Substance Use Disorders are common and result in significant morbidities and mortality. Despite evidence-based treatment availability, multiple barriers exist to care delivery. Because telemedicine offers opportunities to overcome these barriers, the objective of this study was to characterize barriers and facilitators to implementing a mental health and substance use disorder telemedicine program in community obstetric and pediatric clinics. Methods Interviews and site surveys were completed with practices engaged in a Women’s Reproductive Behavioral Health Telemedicine program (N = 6 sites; 18 participants) at the Medical University of South Carolina and telemedicine providers involved in care delivery (N = 4). Using a structured interview guide based on implementation science principles, we assessed program implementation experiences and perceived barriers and facilitators to implementation. A template analysis approach was used to analyze qualitative data within and across groups. Results The primary program facilitator was service demand driven by the lack of available maternal mental health and substance use disorder services. Strong commitment to the importance of addressing these health concerns provided a foundation for successful program implementation yet practical challenges such as staffing, space, and technology support were notable barriers. Services were supported by establishing good teamwork within the clinic and with the telemedicine team. Conclusion Capitalizing on clinics’ commitment to care for women’s needs and a high demand for mental health and substance use disorder services while also addressing resource and technology needs will facilitate telemedicine program success. Study results may have implications for potential marketing, onboarding and monitoring implementation strategies to support clinics engaging in telemedicine programs.

IntroductionThe present systematic review and meta-analysis explores the impacts of cognitive processing therapy (CPT), eye movement desensitization and reprocessing (EMDR), and prolonged exposure (PE) therapy on neural activity underlying the phenomenon of post-traumatic growth for adult trauma survivors.MethodsWe utilized the following databases to conduct our systematic search: Boston College Libraries, PubMed, MEDLINE, and PsycINFO. Our initial search yielded 834 studies for initial screening. We implemented seven eligibility criteria to vet articles for full-text review. Twenty-nine studies remained for full-text review after our systematic review process was completed. Studies were subjected to several levels of analysis. First, pre-and post- test post-traumatic growth inventory (PTGI) scores were collected from all studies and analyzed through a forest plot using Hedges’ g. Next, Montreal Neurological Institute (MNI) coordinates and t-scores were collected and analyzed using an Activation Likelihood Estimation (ALE) to measure brain function. T-scores and Hedges’ g values were then analyzed using Pearson correlations to determine if there were any relationships between brain function and post-traumatic growth for each modality. Lastly, all studies were subjected to a bubble plot and Egger’s test to assess risk of publication bias across the review sample.ResultsForest plot results indicated that all three interventions had a robust effect on PTGI scores. ALE meta-analysis results indicated that EMDR exhibited the largest effect on brain function, with the R thalamus (t = 4.23, p t = 4.19, p r = 0.910, p p = 0.127).DiscussionOur systematic review and meta-analysis showed that CPT, EMDR, and PE each exhibited a robust effect on PTG impacts across the course of treatment. However, when looking closer at comparative analyses of neural activity (ALE) and PTGI scores (Pearson correlation), EMDR exhibited a more robust effect on PTG impacts and brain function than CPT and PE.

The ongoing COVID-19 pandemic has rendered confined spaces as high-risk areas. There is an increasing push to resume in-person activities, for instance, teaching in K-12 and university settings. It becomes important to evaluate the risk of airborne disease transmission while accounting for the physical presence of humans, furniture, and electronic equipment, as well as ventilation. Here, we present a computational framework based on detailed flow physics simulations that allows straightforward evaluation of various seating and operating scenarios to identify risk factors and assess the effectiveness of various mitigation strategies. These scenarios include seating arrangement changes, presence/absence of computer screens, ventilation rate changes, and presence/absence of mask-wearing. This approach democratizes risk assessment by automating a key bottleneck in simulation-based analysis--creating an adequately refined mesh around multiple complex geometries. Not surprisingly, we find that wearing masks (with at least 74% inward protection efficiency) significantly reduced transmission risk against unmasked and infected individuals. The availability of such an analysis approach will allow education administrators, government officials (courthouses, police stations), and hospital administrators to make informed decisions on seating arrangements and operating procedures.

BACKGROUND: WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level.METHODS: We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rate- or time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years.RESULTS: The overall pooled influenza-associated hospitalisation rate was 40.1 (95% confidence interval (CI) = 23.3-69.1) per 100 000 persons, with rates varying substantially by age: 137.8 (95% CI = 70.6-268.7) in children aged 0-4 years and 71.6 (95% CI = 39.9-127.7) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates).CONCLUSIONS: Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years.

SummaryObjectivePatients with refractory epilepsy experience extensive and invasive clinical testing for seizure onset zones treatable by surgical resection. However, surgical resection can fail to provide therapeutic benefit, and patients with neocortical epilepsy have the poorest therapeutic outcomes. This case series studied patients with neocortical epilepsy who were referred for surgical treatment. Prior to surgery, patients volunteered for resting-state functional magnetic resonance imaging (rs-fMRI) in addition to imaging for the clinical standard of care. This work examined the variability of functional connectivity in patients, estimated from rs-fMRI, for associations with surgical outcomes.MethodsThis work examined pre-operative structural imaging, pre-operative rs-fMRI, and post-operative structural imaging from seven epilepsy patients. Review of the clinical record provided Engel classifications for surgical outcomes. A novel method assessed pre-operative rs-fMRI from patients using comparative rs-fMRI from a large cohort of healthy control subjects and estimated Gibbs distributions for functional connectivity in patients compared to healthy controls.ResultsThree patients had Engel classification Ia, one patient had Engel classification IIa, and three patients had Engel classification IV. Metrics for variability of functional connectivity, including absolute differences of the functional connectivity of each patient from healthy control averages and probabilistic scores for absolute differences, were higher for patients classified as Engel IV, for whom epilepsy surgery provided no meaningful improvement.SignificanceThis work continues on-going efforts to use rs-fMRI to characterize abnormal functional connectivity in the brain. Preliminary evidence indicates that the topography of variant functional connectivity in epilepsy patients may be clinically relevant for identifying patients unlikely to have favorable outcomes after epilepsy surgery. Widespread topographic variations of functional connectivity also support the hypothesis that epilepsy is a disease of brain resting-state networks.

Hibernators adjust the expression of torpor behaviourally and physiologically to balance the benefits of energy conservation in hibernation against the physiological and ecological costs. Small fat-storing species, like many cave-hibernating bats, have long been thought to be highly constrained in their expression of hibernation because they must survive winter relying only on endogenous energy stores. We evaluated behavioural microclimate selection in tri-colored bats (Perimyotis subflavus (F. Cuvier, 1832)) across a 3-month hibernation experiment under laboratory conditions. We also opportunistically tested for evidence of acclimatization in torpid metabolic rate (TMR). When given access to gradients in microclimate, bats tended to choose the warmest temperature available (11 °C) while almost completely avoiding the driest condition available (85% relative humidity at 8 °C). Furthermore, bats held at different temperatures over the course of the hibernation showed no differences in TMR when measured under common conditions at the end of hibernation. Taken together, our results suggest that selective pressures to conserve energy during hibernation are not overwhelmingly strong and further support the proposition that optimal expression of hibernation is something less than the maximal expression of hibernation unless the animal is nearing starvation.

Introduction: Latinx children are the fastest-growing ethnic minority of children under the age of 5 years in a tri-county area in the Southeastern United States (US Census, 2018). There are limited culturally and linguistically appropriate school preparedness initiatives in this geographic region. Methods: A cultural and linguistic appropriate program was developed in coordination with the state's largest Latinx advocacy organization and two patient-centered pediatric medical homes (PCPMHs) after securing extramural grant funding for an evidenced-based home visitation program using skilled community health workers (CHWs) aimed at Latinx children at the age of 0–5 years and their caregivers. The program includes developmental screenings using the Ages & Stages Questionnaires®, Third Edition (ASQ®-3), CHW role modeling of developmentally appropriate play, early literacy, connection to resources, oral health, nutrition, and physical activity. Results: Of the 103 unique children represented in this programmatic evaluation that received an initial and follow-up ASQ®-3 developmental screening, paired t-tests indicate statistically significant improvement in mean scores from the first to second ASQ®-3 in all five major developmental domains with the largest gains represented in the communication and fine motor skill domains. Conclusion: This evaluation suggests that low-frequency home visits from skilled CHWs can have a beneficial effect on development in early childhood. PPCMHs can serve as a hub for these community-based programs.

Background and ObjectivesLate-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) affects a significant number of individuals. Head injury is also a risk factor for acquired epilepsy, but the degree to which prior head injury may contribute to LOE is less well understood. Our objective was to determine the association between head injury and subsequent development of LOE.MethodsIncluded were 8,872 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study with continuous Centers for Medicare Services fee-for-service (FFS) coverage (55.1% women, 21.6% Black). We identified head injuries through 2018 from linked Medicare fee for service claims for inpatient/emergency department care, active surveillance of hospitalizations, and participant self-report. LOE cases through 2018 were identified from linked Medicare FFS claims. We used Cox proportional hazards models to evaluate associations of head injury with LOE, adjusting for demographic, cardiovascular, and lifestyle factors.ResultsThe adjusted hazard ratio (HR) for developing LOE after a history of head injury was 1.88 (95% confidence interval [CI] 1.44–2.43). There was evidence for dose–response associations with greater risk for LOE with increasing number of prior head injuries (HR 1.37, 95% CI 1.01–1.88 for 1 prior head injury and HR 3.55, 95% CI 2.51–5.02 for 2+ prior head injuries, compared to no head injuries) and with more severe head injury (HR 2.53, 95% CI 1.83–3.49 for mild injury and HR 4.90, 95% CI 3.15–7.64 for moderate/severe injury, compared to no head injuries). Associations with LOE were significant for head injuries sustained at older age (age ≥67 years: HR 4.01, 95% CI 2.91–5.54), but not for head injuries sustained at younger age (age < 67 years: HR 0.98, 95% CI 0.68–1.41).DiscussionHead injury was associated with increased risk of developing LOE, particularly when head injuries were sustained at an older age, and there was evidence for higher risk for LOE after a greater number of prior head injuries and after more severe head injuries.Classification of EvidenceThis study provides Class I evidence that an increased risk of late-onset epilepsy is associated with head injury and that this risk increases further with multiple and more severe head injuries.

Brain-state transitions are readily apparent from changes in brain rhythms,1 but are difficult to predict, suggestive that the underlying cause is latent to passive recording methods. Among the most important transitions, clinically, are the starts of seizures. We here show that an ‘active probing’ approach may have several important benefits for epileptic management, including by helping predict these transitions. We used mice expressing the optogenetic actuator, channelrhodopsin, in pyramidal cells, allowing this population to be stimulated in isolation. Intermittent stimulation at frequencies as low as 0.033 Hz (period = 30 s) delayed the onset of seizure-like events in an acute brain slice model of ictogenesis, but the effect was lost if stimulation was delivered at even lower frequencies (1/min). Notably, active probing additionally provides advance indication of when seizure-like activity is imminent, revealed by monitoring the postsynaptic response to stimulation. The postsynaptic response, recorded extracellularly, showed an all-or-nothing change in both amplitude and duration, a few hundred seconds before seizure-like activity began—a sufficient length of time to provide a helpful warning of an impending seizure. The change in the postsynaptic response then persisted for the remainder of the recording, indicative of a state change from a pre-epileptic to a pro-epileptic network. This occurred in parallel with a large increase in the stimulation-triggered Ca2+ entry into pyramidal dendrites, and a step increase in the number of evoked postsynaptic action potentials, both consistent with a reduction in the threshold for dendritic action potentials. In 0 Mg2+ bathing media, the reduced threshold was not associated with changes in glutamatergic synaptic function, nor of GABAergic release from either parvalbumin or somatostatin interneurons, but simulations indicate that the step change in the optogenetic response can instead arise from incremental increases in intracellular [Cl−]. The change in the response to stimulation was replicated by artificially raising intracellular [Cl−], using the optogenetic chloride pump, halorhodopsin. By contrast, increases in extracellular [K+] cannot account for the firing patterns in the response to stimulation, although this, and other cellular changes, may contribute to ictal initiation in other circumstances. We describe how these various cellular changes form a synergistic network of positive feedback mechanisms, which may explain the precipitous nature of seizure onset. This model of seizure initiation draws together several major lines of epilepsy research as well as providing an important proof-of-principle regarding the utility of open-loop brain stimulation for clinical management of the condition.