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Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder affecting approximately 4-7% of children and persisting in 2-5% of adults. The core symptoms include pervasive inattention and inappropriate levels of hyperactivity-impulsivity. High-frequency gamma activity has been implicated in the temporal binding of stimulus properties across cortical areas, and is known to be crucial for complex information processing and attentional processes in particular. Thus, we evaluated the amplitude of gamma-frequency neural responses in adults with and those without ADHD, and tested whether stimulant medications, the most common treatment for ADHD, modulate gamma activity in affected adults. Participants underwent two sessions (~75 min apart) of auditory stimulation using stimuli known to elicit 40 Hz gamma-band responses as magnetoencephalography data were acquired. Between sessions, the ADHD group (who were in maintenance therapy) were administered their daily stimulant medication and both groups were told to relax. The primary results indicated that gamma activity was weaker in the ADHD group during session one (pre-drug), but not session two (post-drug), and that gamma activity significantly increased following stimulant administration in adults with ADHD. These results suggest that ADHD is associated with reduced cortical gamma activity and that stimulants may ameliorate this abnormality. [ABSTRACT FROM AUTHOR]

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space.The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment.

Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chimeric antigen receptor (CAR) T cells from allogeneic donors promise "off-the-shelf" availability by overcoming challenges associated with autologous cell manufacturing. However, recipient immunologic rejection of allogeneic CAR-T cells may decrease their in vivo lifespan and limit treatment efficacy. Here, we demonstrate that the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice, extending their in vivo persistence to that of syngeneic humanized mouse-derived CAR-T cells. In turn, genetic knockout (KO) of FKBP prolyl isomerase 1A (FKBP1A), which encodes a protein targeted by both drugs, was necessary to confer CD19-specific CAR-T cells (19CAR) robust functional resistance to these immunosuppressants. FKBP1A KO 19CAR-T cells maintained potent in vitro functional profiles and controlled in vivo tumor progression similarly to untreated 19CAR-T cells. Moreover, immunosuppressant treatment averted in vivo allorejection permitting FKBP1A KO 19CAR-T cell-driven B cell aplasia. Thus, we demonstrate that genome engineering enables immunosuppressant treatment to improve the therapeutic potential of universal donor-derived CAR-T cells., Competing Interests: Declaration of interests C.R.M., A.C.M., P.B.B., A.J.C., F.M.M., M.L.W., J.J.R., L.J.C., C.K., F.L., and B.Y. were employees of Beam Therapeutics when the work was conducted and are shareholders in the company. Beam Therapeutics has filed patent applications based on this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background:  Experiential learning through simulation allows students to apply didactic knowledge to real-world situations. Tabletop simulation allows for the exploration of a variety of topics, including cybersecurity in health care. Due to its low frequency, yet high-risk nature, simulation is a perfect educational modality to practice responding to a cybersecurity attack. As such, the authors designed and executed a tabletop cybersecurity simulation consisting of a prebriefing, four rounds of injects detailing potential cybersecurity breaches that students must address, and structured debriefings that included input from cybersecurity content experts. This simulation was performed in 2018, 2019, 2022, and 2023, during graduate Health Informatics (HI) students' residential visits., Objective:  The simulation allowed opportunities for HI students to apply knowledge of cybersecurity principles to an unfolding tabletop simulation containing injects of scenarios they may encounter in the real world., Methods:  Survey data were used to assess the students' perceptions of the simulation. Topics assessed included overall satisfaction, teamwork and communication, and length of the event. Additionally, in 2022 and 2023, data were collected on psychological safety and whether to include them in future HI residential visits., Results:  Eighty-eight graduate HI students took part in the cybersecurity simulation over four annual residential visits. Most students were satisfied with the event, found it valuable, and could see it impacting their future practice as informaticists. Additionally, students indicated high levels of psychological safety. Multiple students requested that additional simulations be incorporated into the curriculum., Conclusion:  A tabletop cybersecurity simulation was utilized to allow HI students the ability to apply knowledge related to cybersecurity breaches to real-world examples. The simulation's best practices of prebriefing, psychological safety, and structured debriefing with expert feedback were emphasized in the simulation's design and implementation. Students found the simulation valuable and worth including in the curriculum., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Objectives: Quality improvement (QI) and simulation employ complementary approaches to improve the care provided to patients. There is a significant opportunity to leverage these disciplines, yet little is known about how they are utilized in concert. The purpose of this study is to explore how QI and simulation have been used together in health care., Methods: This scoping review includes studies published between 2015 and 2021 in 4 databases: CINAHL, Embase, PubMed, and Scopus., Results: The search yielded 921 unique articles.18 articles met the inclusion criteria and specifically described QI and simulation collaborative projects. Of the 18 articles, 28% focused on improvements in patient care, 17% on educational interventions, 17% on the identification of latent safety threats (LSTs) that could have an impact on clinical care, 11% on the creation of new processes, 11% on checklist creation, and 6% on both LST identification and educational intervention. The review revealed that 61% of the included studies demonstrated a concurrent integration of simulation and QI activities, while 33% used a sequential approach., Conclusions: There is a paucity of studies detailing the robust and synergistic use of QI and simulation. The findings of this review suggest a positive impact on patient safety when QI and simulation are used in tandem. The systematic integration of these disciplines and the use of established reporting guidelines can promote patient safety in practice and in the literature., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mindfulness has long been theorized to benefit emotion regulation, but despite the ubiquity of the claim, there is little empirical evidence demonstrating how mindfulness modulates the neurophysiology of emotion processing. The current study aimed to fill this gap in knowledge by leveraging a novel research approach capable of discretizing mindfulness into distinct states of open monitoring (OM) and focused attention (FA) to distinguish their influence on multimodal subjective and objective measures of emotion processing., Methods: Utilizing a fully within-participant picture viewing state induction protocol ( N  = 30), we compared the effects of OM and FA, rigorously contrasted against an active control, on the visually evoked late positive potential (LPP), a neural index of motivated attention. Bayesian mixed modeling was used to distinguish OM versus FA effects on the early and late sustained LPP while evaluating the influence of subjective arousal ratings as a within-participant moderator of the state inductions., Results: When negative picture trials were retrospectively rated as more subjectively arousing, the OM induction reduced the late sustained LPP response, whereas the FA induction enhanced the LPP., Conclusions: Acute manipulation of OM and FA states may reduce and enhance motivated attention to aversive stimuli during conditions of high subjective arousal, respectively. Functional distinctions between different mindfulness states on emotion processing may be most dissociable after accounting for within-participant variability in how stimuli are appraised. These results support the future potential of the state induction protocol for parsing the neural affective mechanisms that underlie mindfulness training programs and interventions., (© 2024 The Authors.)

Over the past two decades, scientific interest in understanding the relationship between mindfulness and cognition has accelerated. However, despite considerable investigative efforts, pervasive methodological inconsistencies within the literature preclude a thorough understanding of whether or how mindfulness influences core cognitive functions. The purpose of the current study is to provide an initial "proof-of-concept" demonstration of a new research strategy and methodological approach designed to address previous limitations. Specifically, we implemented a novel fully within-subject state induction protocol to elucidate the neurobehavioral influence of discrete mindfulness states-focused attention (FA) and open monitoring (OM), compared against an active control-on well-established behavioral and ERP indices of executive attention and error monitoring assessed during the Eriksen flanker task. Bayesian mixed modeling was used to test preregistered hypotheses pertaining to FA and OM effects on flanker interference, the stimulus-locked P3, and the response-locked ERN and Pe. Results yielded strong but unexpected evidence that OM selectively produced a more cautious and intentional response style, characterized by higher accuracy, slower RTs, and reduced P3 amplitude. Follow-up exploratory analyses revealed that trait mindfulness moderated the influence of OM, such that individuals with greater trait mindfulness responded more cautiously and exhibited higher trial accuracy and smaller P3s. Neither FA nor OM modulated the ERN or Pe. Taken together, our findings support the promise of our approach, demonstrating that theoretically distinct mindfulness states are functionally dissociable among mindfulness-naive participants and that interactive variability associated with different operational facets of mindfulness (i.e., state vs. trait) can be modeled directly., (© 2024. The Psychonomic Society, Inc.)

The literature on adolescent sleep has shown a bidirectional relationship between sleep difficulties and altered eating habits, including emotional eating. However, it is unclear if this relationship is related to preexisting body concerns, or if poor sleep is the prime contributor to emotional eating patterns. This study therefore seeks to examine body dissatisfaction as a moderator of the sleep-emotional eating relationship in an at-risk sample. Adolescents (N = 106) presenting for overnight polysomnography self-reported on time-in-bed, insomnia, body dissatisfaction, and emotional eating. Less time-in-bed was correlated with a greater desire for thinness and greater insomnia severity was related to overall emotional eating and eating in response to anxiety, anger, and frustration and in response to depression. Moderation analyses revealed that the relationships between time-in-bed and eating in response to feeling unsettled (b =  -.002, 95% CI[- .003,  - .001], p < .005) and eating in response to anxiety, anger, and frustration (b =  -.01, 95% CI[- .01,  - .001], p < .05) were exacerbated by worse body dissatisfaction. Optimizing sleep may attenuate the risk for disordered eating, particularly for adolescents with high body dissatisfaction., (© 2024. The Author(s).)

The development of advanced microscopy techniques has ushered in a new era of research as it helps understand biological processes on a deeper, mechanistic, and molecular level like never before. Live-cell fluorescence microscopy has importantly allowed us to visualize subcellular protein localization and incorporation of various fluorophores compatible with living cells in real time. As such, this technique offers valuable insights at the single-cell level and enables us to monitor phenotypic differences that were easily overlooked at a population level. One area of research that has benefited greatly from these advances is the study of the bacterial cell envelope biogenesis and cell division process. In this report, we provide detailed protocols, optimized in our lab, for imaging these processes in the Gram-positive organisms Bacillus subtilis and Staphylococcus aureus., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors declare no conflict of interest.

Chronic sensory loss is a common and undertreated consequence of many forms of neurological injury. Emerging evidence indicates that vagus nerve stimulation (VNS) delivered during tactile rehabilitation promotes recovery of somatosensation. Here, we systematically varied the timing of VNS relative to tactile rehabilitation to determine the paradigm that yields the greatest degree of somatosensory recovery after peripheral nerve injury (PNI). The medial and ulnar nerves in rats were transected, causing chronic sensory loss. Eight weeks after injury, rats were given a VNS implant followed by four weeks of tactile rehabilitation sessions consisting of repeated mechanical stimuli to the previously denervated forepaw. Rats received VNS before, during, or after tactile rehabilitation. Delivery of VNS during rehabilitative training generates robust, significant recovery compared to rehabilitative training without stimulation (56 ± 14% improvement over sham stimulation). A matched amount of VNS before training, immediately after training, or two hours after training is significantly less effective than VNS during rehabilitative training and fails to improve recovery compared to rehabilitative training alone (5 ± 10%, 4 ± 11%, and -7 ± 22% improvement over sham stimulation, respectively). These findings indicate that concurrent delivery of VNS during rehabilitative training is most effective and illustrate the importance of considering stimulation timing for clinical implementation of VNS therapy., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There are wide variations in the gender makeup of speakers at national pediatric emergency medicine (PEM) conferences with no significant change in recent years., Objective: Gender disparities exist among national speakers and award recipients. PEM represents the intersection of pediatrics, a female-dominated specialty with approximately 58% women, and emergency medicine, a male-dominated specialty. We describe the proportion of women speakers and award recipients at two national PEM conferences, the American Academy of Pediatrics (AAP) Section on Emergency Medicine (SOEM) and the Advanced PEM Assembly (APEMA), to the AAP National Conference & Exhibition (NCE), a national pediatric conference., Methods: Data from SOEM and APEMA, obtained from 2016 to 2021 were compared to the 2021 NCE. Invited speakers, abstract presenters, and award recipients were identified. Gender was determined by searching each individual's name for self-identification. Gender proportions were compared across conferences, speaker type, and year., Results: Compared to the NCE, a significantly smaller proportion of women were invited speakers at APEMA (NCE 59.9% vs. APEMA 38.8%, p < 0.001), but similar proportions of women were invited speakers (53.9%, p = 0.178) and awardees at SOEM (50% vs. 50%, p = 1.0). A larger number of women were SOEM abstract presenters than invited speakers (63.3% vs. 53.9%, p = 0.041). Between 2016 and 2021, the proportion of women invited speakers (SOEM, p = 0.744; APEMA, p = 0.947) or abstract presenters (SOEM, p = 0.632) did not significantly change., Conclusions: Compared to NCE, women are underrepresented as speakers at APEMA, but not at SOEM. Abstract presenters are more likely to be women compared to invited speakers. While awards appear equally distributed, recipients do not mirror the proportion of women in PEM. Conference organizers and leaders in PEM should ensure gender equity in national recognition., (© 2023 Society for Academic Emergency Medicine.)

Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs., Competing Interests: Declaration of interests A.R.K. is a co-founder, consultant, and member of the Board of Neurona Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood 1,2 . Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of RhoGEF signalling in human neurons delays morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell-type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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.

Background and Objectives: As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccines become available to children, pediatricians must navigate vaccination discussions in the setting of rapidly changing vaccine recommendations and approvals. We developed and evaluated an educational curriculum for pediatricians to improve their knowledge about COVID-19 vaccines and confidence in communicating with patients and families about COVID-19 vaccines., Methods: Five institutions collaborated to develop an online educational curriculum. Utilizing the collaboration's multidisciplinary expertise, we developed a 3-module curriculum focused on the SARS-CoV-2 virus and vaccine basics, logistics and administration of COVID-19 vaccine, and COVID-19 vaccine communication principles. Surveys administered to clinician participants before and after completion of the curriculum assessed knowledge and confidence; a follow-up survey 1 month after the post-survey assessed persistence of initial findings., Results: A total of 152 pediatric providers participated; 72 completed both pre- and post-surveys. The median knowledge score improved from the pre-survey to the post-survey (79%-93%, P < .001). There was an increase in providers' confidence after completing the curriculum, which persisted in the follow-up survey. In the post-survey, 98% of participants had had the opportunity to discuss the COVID-19 vaccine with patients, and most clinicians reported that the modules decreased apprehension some or significantly., Conclusions: This project demonstrates rapid and feasible deployment of a curriculum providing up-to-date information to front-line clinicians responsible for having complex conversations about COVID-19 vaccine decision-making. Clinicians who completed this curriculum had sustained increased confidence and decreased levels of apprehension when discussing the COVID-19 vaccine., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure: The authors declare no conflict of interest.

Poverty contributes to acute illness, chronic disease and health inequity among millions of Americans, yet health care providers often do not understand the daily experiences of those who live below the poverty line and how it affects their interactions with the health care system. In this narrative, we share healthcare students' stories and reflect on how they account for their experiences of participating in a poverty simulation. Their words come from reflection assignments, and when we read their words, that for a moment, many of our students understand that as a healthcare practitioner, they can make a difference in the life of someone living in poverty. We believe that this experience will inspire our students to make meaningful change as future healthcare professionals. We also believe that the impact on these students goes toward our collective goal as teachers of future healthcare providers to make a difference in our world.

Poverty is a leading cause of numerous health and social inequities in the United States. Educators are increasingly searching for ways to create meaningful learning opportunities about poverty and its profound effect on individuals and communities. In this narrative, we explore our own perspectives as faculty who guide students through a simulated poverty experience. This essay unfolds primarily as a dialogue among us as we make sense of and clarify why we participate in the coordination and facilitation of poverty simulations on our campus and their anticipated benefits for future health care professionals and social service providers.

Background: Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty., Methods: In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models., Results: The median age at BMI rebound was 5.3 years (interquartile range: 3.6-6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83-0.97) and menarche (HR = 0.86; 95% CI = 0.79-0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development., Conclusions: Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

The bacterial division and cell wall ( dcw ) cluster is a highly conserved region of the genome which encodes several essential cell division factors, including the central divisome protein FtsZ. Understanding the regulation of this region is key to our overall understanding of the division process. mraZ is found at the 5' end of the dcw cluster, and previous studies have described MraZ as a sequence-specific DNA binding protein. In this article, we investigate MraZ to elucidate its role in Bacillus subtilis. Through our investigation, we demonstrate that increased levels of MraZ result in lethal filamentation due to repression of its own operon ( mraZ - mraW - ftsL - pbpB ). We observed rescue of filamentation upon decoupling ftsL expression, but not other genes in the operon, from MraZ control. Our data suggest that regulation of the mra operon may be an alternative way for cells to quickly arrest cytokinesis, potentially during entry into the stationary phase and in the event of DNA replication arrest. Furthermore, through time-lapse microscopy, we were able to identify that overexpression of mraZ or depletion of FtsL results in decondensation of the FtsZ ring (Z-ring). Using fluorescent d-amino acid labeling, we also observed that coordinated peptidoglycan insertion at the division site is dysregulated in the absence of FtsL. Thus, we reveal that the precise role of FtsL is in Z-ring maturation and focusing septal peptidoglycan synthesis. IMPORTANCE MraZ is a highly conserved protein found in a diverse range of bacteria, including genome-reduced Mycoplasma . We investigated the role of MraZ in Bacillus subtilis and found that overproduction of MraZ is toxic due to cell division inhibition. Upon further analysis, we observed that MraZ is a repressor of its own operon, which includes genes that encode the essential cell division factors FtsL and PBP2B. We noted that decoupling of ftsL alone was sufficient to abolish MraZ-mediated cell division inhibition. Using time-lapse microscopy, we showed that under conditions where the FtsL level is depleted, the cell division machinery is unable to initiate cytokinesis. Thus, our results pinpoint that the precise role of FtsL is in concentrating septal cell wall synthesis to facilitate cell division.

This study compared different approaches to measuring breast density and breast tissue composition (BTC) in adolescent girls (n = 42, aged 14-16 years) and their mothers (n = 39, aged 36-61 years) from a cohort in Santiago, Chile. Optical spectroscopy (OS) was used to measure collagen, water, and lipid concentrations, which were combined into a percent breast density index (%BDI). A clinical dual-energy X-ray absorptiometry (DXA) system calibrated to measure breast density provided percent fibroglandular volume (%FGV) from manually delineated images. After digitizing mammogram films, the percent mammographic breast density (%MBD) was measured using computer-assisted software. Partial correlation coefficients (r partial ) were used to evaluate associations between breast density measures and BTC from these three different measurement approaches, adjusting for age and body mass index. %BDI from OS was associated with %FGV from DXA in adolescent girls (r partial  = 0.46, p-value = 0.003), but not in mothers (r partial  = 0.17, p-value = 0.32). In mothers, %FGV from DXA was associated with %MBD from mammograms (r partial  = 0.60, p-value < 0.001). These findings suggest that data from OS, DXA, and mammograms provide related but distinct information about breast density and BTC. Future studies should explore how the information provided by these different devices can be used for breast cancer risk prediction in cohorts of adolescent girls and women., (© 2022. The Author(s).)

Background: Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers., Methods: We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother-daughter dyads (recruited 1998-2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters (n = 186) and mothers (n = 175) reached ages 11-20 and 29-55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS., Results: No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content (β daughters  = 0.42, 95% CI = 0.15-0.68; β mothers  = 0.32, 95% CI = 0.05-0.61) and higher optical index (β daughters  = 0.38, 95% CI = 0.12-0.64; β mothers  = 0.38, 95% CI = 0.12-0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05)., Conclusions: Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations., (© 2022. The Author(s).)

M23 family endopeptidases play important roles in cell division and separation in a wide variety of bacteria. Recent studies have suggested that these proteins also contribute to bacterial virulence. However, the biological function of M23 peptidases in pathogenic spirochetes remains unexplored. Here, we describe Borrelia burgdorferi, the bacterial pathogen causing Lyme disease, requires a putative M23 family homolog, BB0761, for spirochete morphology and cell division. Indeed, the inactivation of bb0761 led to an aberrant filamentous phenotype as well as the impairment of B. burgdorferi growth in vitro. These phenotypes were complemented not only with B. burgdorferi bb0761, but also with the mepM gene from E. coli. Moreover, the bb0761 mutant showed a complete loss of infectivity in a murine model of Lyme borreliosis. Resistance of the mutant to osmotic and oxidative stresses was markedly reduced. Our combined results indicate that BB0761 contributes to B. burgdorferi cell division and virulence., (© 2022 John Wiley & Sons Ltd.)

Introduction: Rapid cycle deliberate practice (RCDP) is a relatively new method for delivering simulation for a structured algorithm-based clinical content. We sought to understand how a group of practicing emergency medicine healthcare professionals would perceive RCDP as a learning method., Methods: This was a qualitative study of participants' reactions to RCDP simulation during an orientation process to a new freestanding emergency department using grounded theory. Focus groups were held after simulation sessions to investigate the participants reactions to RCDP as well as the experience of multiple professions participating. Two investigators independently coded the focus group transcripts to detect themes and developed a list of codes, which were then confirmed by consensus. Data were organized into themes with contributing codes., Results: Thirty-one individuals participated in the focus groups including physicians, nurse practitioners, nurses, respiratory therapists, and patient care technicians. Four themes were detected: the procedural components of RCDP, the behavioral response to RCDP, learning through RCDP, and RCDP as interprofessional experience. The participants view of emotions and interruptions and pauses had discrepant interpretation., Conclusions: Participants received RCDP simulation positively. Initial negative reactions to the interruptions and pauses of RCDP dissipated as the simulation progressed. Ultimately, learners agreed that RCDP was extremely effective as compared with traditional simulation for medical resuscitation training because of the authenticity of the multidisciplinary aspect. This suggests that RCDP may be an effective tool for continuing education of practicing healthcare professionals., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Society for Simulation in Healthcare.)

While the epithelial cell cortex displays profound asymmetries in protein distribution and morphology along the apico-basal axis, the extent to which the cytoplasm is similarly polarized within epithelial cells remains relatively unexplored. We show that cytoplasmic organelles within C. elegans embryonic intestinal cells develop extensive apico-basal polarity at the time they establish cortical asymmetry. Nuclei and conventional endosomes, including early endosomes, late endosomes, and lysosomes, become polarized apically. Lysosome-related gut granules, yolk platelets, and lipid droplets become basally enriched. Removal of par-3 activity does not disrupt organelle positioning, indicating that cytoplasmic apico-basal asymmetry is independent of the PAR polarity pathway. Blocking the apical migration of nuclei leads to the apical positioning of gut granules and yolk platelets, whereas the asymmetric localization of conventional endosomes and lipid droplets is unaltered. This suggests that nuclear positioning organizes some, but not all, cytoplasmic asymmetries in this cell type. We show that gut granules become apically enriched when WHT-2 and WHT-7 function is disrupted, identifying a novel role for ABCG transporters in gut granule positioning during epithelial polarization. Analysis of WHT-2 and WHT-7 ATPase mutants is consistent with a WHT-2/WHT-7 heterodimer acting as a transporter in gut granule positioning. In wht-2(-) mutants, the polarized distribution of other organelles is not altered and gut granules do not take on characteristics of conventional endosomes that could have explained their apical mispositioning. During epithelial polarization wht-2(-) gut granules exhibit a loss of the Rab32/38 family member GLO-1 and ectopic expression of GLO-1 is sufficient to rescue the basal positioning of wht-2(-) and wht-7(-) gut granules. Furthermore, depletion of GLO-1 causes the mislocalization of the endolysosomal RAB-7 to gut granules and RAB-7 drives the apical mispositioning of gut granules when GLO-1, WHT-2, or WHT-7 function is disrupted. We suggest that ABC transporters residing on gut granules can regulate Rab dynamics to control organelle positioning during epithelial polarization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context: This review synthesizes the findings of previous research studies on the cardiovascular and metabolic benefits of aerobic exercise for individuals with tetraplegia secondary to spinal cord injury. They are often less active due to muscular paralysis, sensory loss, and sympathetic nervous system dysfunction that result from injury. Consequently, these persons are at higher risk for exercise intolerance and secondary health conditions., Objective: To evaluate the evidence concerning efficacy of aerobic exercise training for improving health and exercise performance in persons with tetraplegia from cervical injury., Methods: The search engines PubMed and Google Scholar were used to locate published research. The final 75 papers were selected on the basis of inclusion criteria. The studies were then rank-ordered using Physiotherapy Evidence Database., Results: Studies combining individuals with tetraplegia and paraplegia show that voluntary arm-crank training can increase mean peak power output by 33%. Functional electrical stimulation leg cycling was shown to induce higher peak cardiac output and stroke volume than arm-crank exercise. A range of peak oxygen uptake (VO 2peak ) values have been reported (0.57-1.32 L/min). Both VO 2peak and cardiac output may be enhanced via increased muscle pump in the legs and venous return to the heart. Hybrid exercise (arm-crank and functional electrical stimulation leg cycling) can result in greater peak oxygen uptake and cardiovascular responses., Conclusion: Evidence gathered from this systematic review of literature is inconclusive due to the lack of research focusing on those with tetraplegia. Higher power studies (level 1-3) are needed with the focus on those with tetraplegia.

The division and cell wall ( dcw ) cluster is a highly conserved region of the bacterial genome consisting of genes that encode several cell division and cell wall synthesis factors, including the central division protein FtsZ. The region immediately downstream of ftsZ encodes the ylm genes and is conserved across diverse lineages of Gram-positive bacteria and Cyanobacteria In some organisms, this region remains part of the dcw cluster, but in others, it appears as an independent operon. A well-studied protein coded from this region is the positive FtsZ regulator SepF (YlmF), which anchors FtsZ to the membrane. Recent developments have shed light on the importance of SepF in a range of species. Additionally, new studies are highlighting the importance of the other conserved genes in this neighborhood. In this minireview, we aim to bring together the current research linking the ylm region to cell division and highlight further questions surrounding these conserved genes., (Copyright © 2021 American Society for Microbiology.)

Purpose: Studies have evaluated the application of perfusion MR for predicting survival in patients with astrocytic brain tumors, but few of them statistically adjust their results to reflect the impact of the variability of treatment administered in the patients. Our aim was to analyze the association between the perfusion values and overall survival time, with adjustment for various clinical factors, including initial treatments and follow-up treatments., Materials and Methods: This study consisted of 51 patients with astrocytic brain tumors who underwent perfusion-weighted MRI with MultiHance® at a dose of 0.1 mmol/kg prior to initial surgery. We measured the mean rCBV, the 5% & 10% maximum rCBV, and the variation of rCBV in the tumors. Comparisons were made between patients with and without 2-year survival using two-sample t-test or Wilcoxon rank-sum test for the continuous data, or chi-square and Fisher exact tests for categorical data. The multivariate cox-proportional hazard regression was fit to evaluate the association between rCBV and overall survival time, with adjustment for clinical factors., Results: Patients who survived less than 2 years after diagnosis had a higher mean and maximum rCBV and a larger variation of rCBV. After adjusting for clinical factors including therapeutic measures, we found no significant association of overall survival time within 2 years with any of these rCBV values., Conclusions: Although patients who survived less than 2 years had a higher mean and maximum rCBV and a larger variation of rCBV, rCBV itself may not be used independently for predicting 2-year survival of patients with astrocytic brain tumors., Competing Interests: The funding from Bracco Diagnostics, Inc. does not alter our adherence to PLOS ONE policies on sharing data and materials.

OBJECTIVE. Primary CNS posttransplant lymphoproliferative disorder (PTLD) may present as multiple contrast-enhancing intraaxial lesions, often with central necrosis and surrounding edema. This imaging appearance is similar to the pattern seen in brain metastases. The purpose of this study was to find differences in the radiologic features of primary CNS PTLD lesions and brain metastases. MATERIALS AND METHODS. We retrospectively reviewed the radiologic findings of 51 primary CNS PTLD lesions in 10 patients and 156 metastatic brain lesions in 25 patients. Lesion size, multifocality, location, necrosis, hemorrhage, perilesional vasogenic edema, contrast enhancement, and diffusion and perfusion features were evaluated. We used the chi-square test or Fisher exact test when appropriate to compare the findings between primary CNS PTLD lesions and brain metastases. RESULTS. Primary CNS PTLD lesions occur in the deep gray matter and periventricular locations more frequently than brain metastases ( p < 0.0001) and are not present at the gray and white matter junctions and vascular border zones as commonly as brain metastases are ( p < 0.0001). Primary CNS PTLD tends to have less frequent hemorrhage ( p < 0.0001), more restricted diffusion ( p = 0.001), and lower perfusion ( p = 0.002) than brain metastases. We did not find statistically significant differences between primary CNS PTLD and brain metastases for lesion size, multifocality, necrosis, and perilesional edema. CONCLUSION. The imaging characteristics of primary CNS PTLD overlap considerably with those of brain metastases, but there are significant differences between primary CNS PTLD lesions and brain metastases in lesion location, diffusion and perfusion features, and tendency to hemorrhage.

Background: Incidental findings are a well-known complication of imaging studies done for both diagnostic and research purposes. Little is known about the rates and types of incidental findings found on brain MRI in patients with HIV infection, who may be at risk for HIV-Associated Neurocognitive Disorders (HAND)., Methods: The parent study included 108 adults with HIV infection and 125 demographically-matched uninfected controls who completed MRI and neuropsychological testing. Incidental findings were classified by the study team as vascular, neoplastic, congenital, other neurologic, or non-neurologic. Categorical measures were compared using Pearson chi-square tests; continuous measures were compared using t-tests., Results: Among participants with HIV infection, 36/108 (33%) had incidental findings compared to 33/125 (26%) controls (p = 0.248). Rates of incidental findings were significantly correlated with increasing age in both participants with HIV infection (p = 0.013) and controls (p = 0.022). We found no correlation between presence of incidental findings and sex or race/ethnicity among either cohort, and no correlation with CD4 count or HAND status for the HIV-infected cohort., Conclusions: Incidental findings were common in both participants with HIV infection and controls, at higher rates than previously reported in healthy populations. There was no significant difference in prevalence between the groups.

Objective: By looking at how the accuracy of preoperative brain mapping methods vary according to differences in the distance from the activation clusters used for the analysis, the present study aimed to elucidate how preoperative functional neuroimaging may be used in such a way that maximizes the mapping accuracy., Methods: The eloquent function of 19 patients with a brain tumor or cavernoma was mapped prior to resection with both functional MRI (fMRI) and magnetoencephalography (MEG). The mapping results were then validated using direct cortical stimulation mapping performed immediately after craniotomy and prior to resection. The subset of patients with equivalent MEG and fMRI tasks performed for motor (n = 14) and language (n = 12) were evaluated as both individual and combined predictions. Furthermore, the distance resulting in the maximum accuracy, as evaluated by the J statistic, was determined by plotting the sensitivities and specificities against a linearly increasing distance threshold., Results: fMRI showed a maximum mapping accuracy at 5 mm for both motor and language mapping. MEG showed a maximum mapping accuracy at 40 mm for motor and 15 mm for language mapping. At the standard 10-mm distance used in the literature, MEG showed a greater specificity than fMRI for both motor and language mapping but a lower sensitivity for motor mapping. Combining MEG and fMRI showed a maximum accuracy at 15 mm and 5 mm-MEG and fMRI distances, respectively-for motor mapping and at a 10-mm distance for both MEG and fMRI for language mapping. For motor mapping, combining MEG and fMRI at the optimal distances resulted in a greater accuracy than the maximum accuracy of the individual predictions., Conclusions: This study demonstrates that the accuracy of language and motor mapping for both fMRI and MEG is heavily dependent on the distance threshold used in the analysis. Furthermore, combining MEG and fMRI showed the potential for increased motor mapping accuracy compared to when using the modalities separately.Clinical trial registration no.: NCT01535430 (clinicaltrials.gov).

Investigations of factors influencing cell division and cell shape in bacteria are commonly performed in conjunction with high-resolution fluorescence microscopy as observations made at a population level may not truly reflect what occurs at a single cell level. Live-cell timelapse microscopy allows investigators to monitor the changes in cell division or cell morphology which provide valuable insights regarding subcellular localization of proteins and timing of gene expression, as it happens, to potentially aid in answering important biological questions. Here, we describe our protocol to monitor phenotypic changes in Bacillus subtilis and Staphylococcus aureus using a high-resolution deconvolution microscope. The objective of this report is to provide a simple and clear protocol that can be adopted by other investigators interested in conducting fluorescence microscopy experiments to study different biological processes in bacteria as well as other organisms.

Purpose: To evaluate the incidence of major hemorrhage after image-guided percutaneous chest tube placement in patients with an abnormal international normalized ratio (INR) measured before the procedure., Materials and Methods: Between January 2013 and September 2017, 49 image-guided percutaneous chest tubes were placed in 45 adult patients who had an elevated INR of greater than 1.6. Data collected included routine serum pre-procedure coagulation studies, indication for chest tube placement, insertion technique, size of chest tube, and presence of complications after drain placement. Major bleeding complications were defined using the Society of Interventional Radiology classification system., Results: Mean patient age was 62 years (range, 22-94 years), with median American Society of Anesthesiologists score of 4. Mean INR was 2.1 (range, 1.7-3), with 21 (43%) procedures with an INR between 1.7 and 1.9, 20 (41%) procedures with an INR between 2.0 and 2.4, and 8 (16%) procedures with an INR between 2.5 and 3.0. Computed tomography guidance was used for 27 (55%) procedures; ultrasound guidance was used for 22 (45%) procedures. Median size of chest tube was 10 Fr (range, 8-14 Fr) used in 27 (55%) procedures. No major bleeding complications were observed. There was a small, significant decrease in mean hemoglobin after the procedure (mean = 0.9g/dL; P < .0001), which correlated to increasing chest tube size (P = .0269)., Conclusions: No major bleeding complications were observed after image-guided percutaneous chest tube placement in patients with an elevated INR. Major bleeding complications in these patients may be safer than initially considered, and this study encourages the conduct of larger trials for further evaluation., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Positive interprofessional (IP) collaboration is an expectation in healthcare to ensure positive patient care outcomes, and IP faculty development is one way to promote self-efficacy gains. Our pilot study assessed interprofessional behaviors and positive interprofessional perceptions with faculty/staff using two interventions. We hypothesized that increased interprofessional faculty development in simulation would have a positive effect on faculty/staff behavior and would result in increased positivity regarding interprofessional behaviors. We collected data on positive IP perceptions. The interventions included standard and intensive faculty development in simulation as compared to a control. Our mixed-method study design consisted of qualitative and quantitative assessments, including focus group interviews and demographics and Interdisciplinary Education Perception Scale (IEPS) questionnaires. Assessments occurred at baseline, 1-3 months and 3-6 months. Data suggested better retention of positive interprofessional perceptions in the intensive training group; however, all groups had a gradual decline in positive interprofessional perceptions. Our outcomes contribute to the literature focused on improved collaborative patient care.

Reproduction in the bacterial kingdom predominantly occurs through binary fission-a process in which one parental cell is divided into two similarly sized daughter cells. How cell division, in conjunction with cell elongation and chromosome segregation, is orchestrated by a multitude of proteins has been an active area of research spanning the past few decades. Together, the monumental endeavors of multiple laboratories have identified several cell division and cell shape regulators as well as their underlying regulatory mechanisms in rod-shaped Escherichia coli and Bacillus subtilis , which serve as model organisms for Gram-negative and Gram-positive bacteria, respectively. Yet our understanding of bacterial cell division and morphology regulation is far from complete, especially in noncanonical and non-rod-shaped organisms. In this review, we focus on two proteins that are highly conserved in Gram-positive organisms, DivIVA and its homolog GpsB, and attempt to summarize the recent advances in this area of research and discuss their various roles in cell division, cell growth, and chromosome segregation in addition to their interactome and posttranslational regulation., (Copyright © 2019 American Society for Microbiology.)